APOL1 INHIBITORS AND METHODS OF USE

Abstract

As used herein, a compound of formula (II): TIFF2025503737001579.tif73165 or a stereoisomer or tautomer thereof, or a pharma- ceutically acceptable salt of any of the foregoing, 1 , R 2 , R 3 , L 1 , L 2 , L 3 , R 4 , X 1 , X 2 , X 3 , and X 4 (wherein R is as defined herein). Also provided are methods of preparing a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharma- ceutically acceptable salt of any of the foregoing. Also provided are methods of inhibiting APOL1 and methods of treating an APOL1-mediated disease, disorder, or condition in an individual.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application Serial No. 63 / 300,592, filed January 18, 2022, U.S. Provisional Application Serial No. 63 / 311,668, filed February 18, 2022, U.S. Provisional Application Serial No. 63 / 332,553, filed April 19, 2022, U.S. Provisional Application Serial No. 63 / 400,359, filed August 23, 2022, and U.S. Provisional Application Serial No. 63 / 422,341, filed November 3, 2022, each of which is incorporated by reference in its entirety herein. [Background technology]

[0002] Apolipoprotein L1 (APOL1) is a pore-forming innate immune factor that protects individuals against trypanosome parasites (Vanhamme, L. et al. Nature (2003) 422, 83-87). A secreted form of APOL1 circulates in the blood as part of a unique high-density lipoprotein (HDL) complex known as trypanosome lytic factor (TLF) (Rifkin, MR Proc. Natl. Acad. Sci. USA (1978) 75, 3450-3454; Raper, J. et al. Infect. Immun. (1999) 67, 1910-1916). TLF is internalized by the parasite via endocytosis (Hager, K Met al. J. Cell Biol. (1994) 126, 155-167). In trypanosomes, APOL1 forms a cation pore, leading to ion flux, swelling, and eventual lysis (Rifkin, MR Exp. Parasitol. (1984) 58, 81-93; Molina-Portela, MP et al. Mol. Biochem. Parasitol. (2005) 144, 218-226; Perez-Morga, D. et al. Science. (2005) 309, 469-472; Thomson, R. & Finkelstein, A. Proc. Natl. Acad. Sci. USA. (2015) 112, 2894-2899).

[0003] Some Trypanosoma brucei subspecies (Tbrhodesiense and Tbgambiense) have developed resistance mechanisms to APOL1-dependent killing (Pays, E. et al. Nat. Rev. Microbiol. (2014) 12, 575-584). Positive selection has led to the development of APOL1 variants G1 (S342G, I384M) and G2 (N388Δ, Y389Δ) that can counteract these resistance mechanisms (Genovese, G. et al. Science. (2010) 329, 841-845). However, individuals with any binary combination of these variants (G1 / G1, G2 / G2, or G1 / G2) are at increased risk of focal segmental glomerular sclerosis (FSGS), kidney disease caused by hypertension, human immunodeficiency virus-associated nephropathy (HIVAN) (Genovese, G. et al. Science. (2010) 329, 841-845; Tzur, S. et al. Hum. Genet. (2010) 128, 345-350; Kopp, J.B. et al. J. Am. Soc. Nephrol. (2011) 22, 2129-2137), sickle cell nephropathy (Ashley-Koch, A.E. et al. Br. J. Haematol. (2011) 155, 386-394), lupus nephritis (Freedman, B.I. et al. Arthritis Rheumatol. (2014) 66, 390-396) and an increased rate of glomerular filtration rate (GFR) in diabetic kidney disease (Parsa, A. et al. N. Engl. J. Med. (2013) 369, 2183-2196). APOL1 high-risk genotypes have been associated with COVID-19-associated nephropathy and other viral nephropathy (Shetty, A. et al. J. Am. Soc. Nephrol. (2021) 32, 33-40; Chang, J. Het al. Am. J. Kidney Dis. (2019) 73, 134-139).Furthermore, reduced kidney allograft survival has been observed after deceased-donor kidney transplants from donors with APOL1 high-risk genotypes (Freedman, BI et al. Transplantation. (2016) 100, 194-202). Having two APOL1 risk alleles also increases the risk of preeclampsia (Reidy, KJ et al. Am. J. Hum. Genet. (2018) 103, 367-376) and sepsis (Chaudhary, NS et al. Clin. J. Am. Soc. Nephrol. (2019) 14, 1733-1740). There are no approved therapies for APOL1-associated nephropathy, and patients are treated based on the standard of care for their underlying form of chronic kidney disease. This creates a clear unmet need for targeted therapies for people with APOL1 high-risk genotypes. Numerous studies have shown that APOL1 risk variants are toxic when overexpressed in human cells (Wan, G. et al. J. Biol. Chem. (2008) 283, 21540-21549; Lan, X. et al. Am. J. Physiol. Renal Physiol. (2014) 307, F326-F336; Olabisi, OA et al. Proc. Natl. Acad. Sci. USA. (2016) 113, 830-837; Ma, L. et al. J. Am. Soc. Nephrol. (2017) 28, 1093-1105; Lannon, H. et al. Kidney Int. (2019) 96, 1303-1307). Recent findings suggest that this toxicity is related to the pore function of APOL1 (Giovinazzo, JA et al. eLife. (2020) 9, e51185). Thus, there is a need to develop compounds suitable for inhibiting APOL1 activity and methods for using such compounds to inhibit APOL1 activity. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Vanhamme, L. et al. Nature (2003) 422, 83 - 87 [Non - Patent Document 2] Rifkin, M. R. Proc. Natl. Acad. Sci. USA. (1978) 75, 3450 - 3454 [Non - Patent Document 3] Raper, J. et al. Infect. Immun. (1999) 67, 1910 - 1916 [Non - Patent Document 4] Hager, K. M. et al. J. Cell Biol. (1994) 126, 155 -​​​​​​​​​​​​​​​​​​​​​​​​​​​​​The present disclosure describes compounds and compositions that may be useful for treating various chronic kidney diseases, such as APOL1-mediated diseases, including FSGS, hypertension-related kidney disease, HIV / AIDS, sickle cell nephropathy, lupus nephritis, diabetic kidney disease, viral nephropathy, COVID-19-associated nephropathy, and APOL1-associated nephropathy. The compounds and compositions may also treat other APOL1-mediated disorders, such as preeclampsia and sepsis. Additionally, in individuals with a high-risk APOL1 genotype, the disclosed compounds may prevent the onset of non-diabetic kidney disease and / or delay the progression of any form of chronic kidney disease. The disclosed chemical entities may also prevent and / or delay progressive kidney allograft loss in patients who have received kidney transplants from donors with a high-risk APOL1 genotype.

[0006] In one embodiment, a compound of formula (II): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 If present, each occurrence independently represents halo, -CN, C 1-6 Alkoxy, and C 1-6 is selected from the group consisting of alkyl, R 1 C 1-6 the alkoxy is optionally substituted with one or more halo; R 1 C 1-6 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-6 Alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; R 2 C 1-6 Alkyl is a group consisting of one or more deuterium, halo, -OH, -NH2, or C1-6 optionally substituted with alkoxy; R 2 C 3-10 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-6 is alkyl; L 1 is C 1-6 is alkylene, L 1 C 1-6 Alkylene is a group consisting of one or more deuterium or C 1-6 optionally substituted with alkyl; C 1-6 Alkyl is one or more -OH or C 1-6 optionally further substituted with alkoxy; L 2 is O or N(R x ) and R x is H or C 1-6 is alkyl; (1)L 3 is absent or O, C 3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 is alkylene, L 3 C 3-10 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; L 3 C 1-6 Alkylene is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; C 1-6 The alkyl is optionally substituted with one or more -OH; L 3 3-10 membered heterocyclyl is one or more -OH or C 1-6 optionally substituted with alkyl; X 1 and X 2 are each independently N or C(R 5 ) and; R 4teeth, (i)-S(O)2-R a ; (ii) 5- to 20-membered heteroaryl, where R 4 The 5- to 20-membered heteroaryl may have one or more C 1-6 optionally substituted with alkyl; (iii)-N(R d )2, and R d is independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-6 alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-6 alkyl)2, and C 1-6 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-6 alkyl, or a 3- to 10-membered heterocycle; R e is optionally substituted with one or more oxo, or both R e together with the N to which they are attached form a 3- to 10-membered heterocyclyl; 3- to 10-membered heterocyclyl may be one or more of halo, oxo, -OH, NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-6 Alkyl, -OH, oxo or -S(O)R a 3- to 10-membered heterocyclyl optionally substituted with (vii)-S(O)-N(C 1-6 alkyl)-(C 1-6 alkyl), (viii)-CN, (ix)-(CH2) q OH, where q is an integer from 0 to 6; (x)-C(O)-C 1-6 alkyl, or (xi)-P(O)(C 1-6 alkyl)2; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b is optionally replaced by R b is independently, at each occurrence, -OH, halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl can be one or more of halo, OH, -S(O)2-C 1-6 Alkyl, or C 3-10 optionally substituted with cycloalkyl; R b C 1-6 Alkyl C 3-10 Cycloalkyl is one or more C 1-6 optionally further substituted with alkyl or —OH; R b C 3-10 Cycloalkyl is a group consisting of one or more -OH, C 3-10 Cycloalkyl, or C 1-6 optionally substituted with alkyl; R b C3-10 Cycloalkyl C 1-6 the alkyl is optionally further substituted with one or more -OH, deuterium, or halo; A 5- to 20-membered heteroaryl may have one or more R c is optionally replaced by R c is independently present in each occurrence, halo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R c C 1-6 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl; R c C 3-10 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; R c 3-10 membered heterocyclyl is one or more -OH or C 1-6 optionally substituted with alkyl; R c 3- to 10-membered heterocyclyl C 1-6 The alkyl is optionally further substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 C optionally substituted with alkyl 1-6 Alkyl, (ii) one or more -OH, -C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6alkyl)2, or -C(O)-C 3-10 Heterocyclyl, or C 1-6 C optionally substituted with alkyl 3-10 cycloalkyl, C 1-6 alkyl optionally substituted with one or more -OH; (iii) one or more C 1-6 a 3- to 10-membered heterocyclyl optionally substituted with alkyl, or (iv) NH(C 1-6 alkyl); R 5 is independently, at each occurrence, H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is an alkoxy; R 5 C 1-6 the alkyl is optionally substituted with one or more halo or -OH; R 5 C 1-6 The alkoxy is optionally substituted with one or more halo; X 3 is N or C(R 6 ) and; X 4 is N or C(R 7 ) and; R 6 and R 7 are each independently H or halo. is provided.

[0007] In one embodiment, the compound of formula (I'): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 If present, each occurrence independently represents halo, -CN, C1-6 Alkoxy, or C 1-6 is selected from the group consisting of alkyl, R 1 C 1-6 the alkoxy is optionally substituted with one or more halo; R 1 C 1-6 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-6 Alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; R 2 C 1-6 Alkyl is one or more of halo, -OH, -NH2, or C 1-6 optionally substituted with alkoxy; R 2 C 3-10 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-6 is alkyl; L 1 is C 1-6 alkylene, and L 1 C 1-6 Alkylene is one or more C 1-6 optionally substituted with alkyl, C 1-6 Alkyl is one or more -OH or C 1-6 optionally further substituted with alkoxy; L 2 is O or N(R x ) and R x is H or C 1-6 is alkyl; (1)L 3 is absent or O, C 3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 is alkylene, C 3-10 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; L 3 C1-6 Alkylene is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; The 3- to 10-membered heterocyclyl is optionally substituted with one or more -OH; X 1 and X 2 are each independently N or C(R 5 ) and; R 4 teeth, (i)-S(O)2-R a ; (ii) 5- to 20-membered heteroaryl, where R 4 The 5- to 20-membered heteroaryl may have one or more C 1-6 optionally substituted with alkyl; (iii)-N(R d )2, and R d is independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-6 alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-6 alkyl)2, and C 1-6 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-6 alkyl, a 3- to 10-membered heterocycle, the 3- to 10-membered heterocycle being optionally substituted with one or more oxo, or both R e together with the N to which they are attached to form a 3- to 10-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-6 Alkyl, -OH, oxo, or -S(O)R a 3- to 10-membered heterocyclyl optionally substituted with (vii)-S(O)-N(C 1-6 alkyl)-(C 1-6 alkyl), (viii)-CN, (ix)-(CH2) q OH, where q is an integer from 0 to 6; (x)-C(O)-C 1-6 alkyl, or (xi)-P(O)(C 1-6 alkyl)2; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b optionally substituted with R b is, independently at each occurrence, halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl can be one or more of halo, OH, -S(O)2-C 1-6 Alkyl, or C 3-10 optionally substituted with cycloalkyl; R b C 1-6 Alkyl C 3-10 Cycloalkyl is one or more C 1-6 optionally further substituted with alkyl or —OH; Rb C 3-10 Cycloalkyl is a group consisting of one or more -OH, C 3-10 Cycloalkyl, or C 1-6 optionally substituted with alkyl; R b C 3-10 Cycloalkyl C 1-6 The alkyl is optionally further substituted with one or more -OH; A 5- to 20-membered heteroaryl may have one or more R c optionally substituted with R c is independently present in each occurrence, halo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R c C 1-6 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl; R c C 3-10 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; R c 3-10 membered heterocyclyl is one or more -OH or C 1-6 optionally substituted with alkyl; R c 3- to 10-membered heterocyclyl C 1-6 The alkyl is optionally further substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 C optionally substituted with alkyl 1-6 Alkyl, (ii) one or more -OH, -C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, or -C(O)-C 3-10 Heterocyclyl, or C 1-6 C optionally substituted with alkyl 3-10 Cycloalkyl, C 1-6 Alkyl is optionally substituted with one or more -OH, or (iii) one or more C 1-6 a 3- to 10-membered heterocyclyl optionally substituted with alkyl; R 5 is independently, at each occurrence, H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH, and R 5 C 1-6 The alkoxy is optionally substituted with one or more halo; R 6 and R 7 are each independently H or halo. is provided.

[0008] In one embodiment, a compound of formula (I): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 is, if present, independently at each occurrence halo, -CN, C 1-6 Alkoxy or -C 1-6 is selected from the group consisting of alkyl, R 1 C1-6 the alkoxy is optionally substituted with one or more halo; R 1 C 1-6 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-6 Alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; R 2 C 1-6 Alkyl is one or more of halo, -OH, -NH2, or C 1-6 optionally substituted with alkoxy; R 2 C 3-10 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-6 is alkyl; L 1 is C 1-6 alkylene, and L 1 C 1-6 Alkylene is one or more C 1-6 optionally substituted with alkyl, C 1-6 Alkyl is one or more -OH or C 1-6 optionally further substituted with alkoxy; L 2 is O or N(R x ) and R x is H or C 1-6 is alkyl; (1)L 3 is absent or O, C 3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 is alkylene, L 3 C 1-6 Alkylene is one or more C 1-6 optionally substituted with alkyl; The 3- to 10-membered heterocyclyl is optionally substituted with one or more -OH; X 1 and X 2are each independently N or C(R 5 ) and; R 4 teeth, (i)-S(O)2-R a , (ii) 5- to 20-membered heteroaryl, where R 4 The 5- to 20-membered heteroaryl may have one or more C 1-6 optionally substituted alkyl; (iii)-N(R d )2, and R d is independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-6 alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-6 alkyl)2, where R d C 1-6 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-6 alkyl, a 3- to 10-membered heterocycle, the 3- to 10-membered heterocycle being optionally substituted with one or more oxo, or both R e together with the N to which they are attached to form a 3- to 10-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-6 3- to 10-membered heterocyclyl optionally substituted with alkyl or oxo; (vii)-S(O)-N(C 1-6 alkyl)-(C 1-6 alkyl), or (viii) -CN; or (2)L 3 is non-existence; X1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b optionally substituted with R b is, independently at each occurrence, halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl is one or more halo, OH, or -S(O)2-C 1-6 optionally substituted with alkyl; R b C 3-10 cycloalkyl is optionally substituted with one or more -OH; A 5- to 20-membered heteroaryl may have one or more R c optionally substituted with R c is independently present in each occurrence, halo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R c C 1-6 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl; Rc C 3-10 The cycloalkyl is optionally substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 C optionally substituted with alkyl 1-6 alkyl, or (ii) one or more -OH, -C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -C(O)-C 3-10 Heterocyclyl, or C 1-6 C optionally substituted with alkyl 3-10 Cycloalkyl, C 1-6 Alkyl is optionally substituted with one or more -OH, or (iii) one or more C 1-6 a 3- to 10-membered heterocyclyl optionally substituted with alkyl; R 5 is independently, at each occurrence, H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 Alkyl is optionally substituted with one or more halo or -OH, and 1-6 The alkoxy is optionally substituted with one or more halo; R 6 and R 7 are each independently H or halo. is provided.

[0009] Any embodiment provided herein of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, is also an embodiment of a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0010] Any embodiment provided herein of a compound of formula (I) or (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, is also an embodiment of a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0011] In one aspect, provided herein is a compound of formula (IA): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein n is 1 or 2; m, p, R 1 , R 2 , R 3 , L 1 , L 3 , R 4 , X 1 , X 2 , R 6 , and R 7 In another variation, m, p, R of formula (IA) are as defined elsewhere herein. 1 , R 2 , R 3 , L 1 , L 3 , R 4 , X 1 , X 2 , R 6 , and R 7is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0012] In one aspect, provided herein is a compound of formula (IB): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , L 3 , R 4 , R 5 , R 6 , and R 7 In another variation, m, p, R of formula (IB) are as defined elsewhere herein. 1 , R 2 , R 3 , L 1 , L 3 , R 4 , R 5 , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0013] In one aspect, provided herein is a compound of formula (IC): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , L 3 , R 4 , and R5 In another variation, m, p, R of formula (IC) are provided. 1 , R 2 , R 3 , L 1 , L 3 , R 4 , and R 5 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0014] In one aspect, provided herein is a compound of formula (ID): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , L 3 , and R 4 In another variation, m, p, R of formula (ID) are as defined elsewhere herein. 1 , R 2 , R 3 , L 1 , L 3 , and R 4 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0015] In one aspect, provided herein are compounds of formula (IE): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R2 , R 3 , L 1 , X 2 , R 6 , R 7 and ring A are as defined elsewhere herein. In another variation, m, p, R of formula (IE) are provided. 1 , R 2 , R 3 , L 1 , X 2 , R 6 , R 7 and ring A are as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0016] In one aspect, provided herein is a compound of formula (IF): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , R 5 and ring A are as defined elsewhere herein. In another variation, m, p, R of formula (IF) are 1 , R 2 , R 3 , L 1 , R 5 and ring A are as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0017] In one aspect, provided herein is a compound of formula (IG): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 and ring A are as defined elsewhere herein. In another variation, m, p, R of formula (IG) are provided. 1 , R 2 , R 3 , L 1 and ring A are as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0018] In one aspect, provided herein is a compound of formula (II-A): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , X 2 , X 3 , X 4 and ring A is as defined elsewhere herein).

[0019] In one aspect, provided herein is a pharmaceutical composition comprising: (i) a compound of formula (I), or any embodiment or variation thereof, e.g., a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients. In another variation, provided herein is a pharmaceutical composition comprising: (i) a compound of formula (I'), or any embodiment or variation thereof, e.g., a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients. In another variation, provided herein is a pharmaceutical composition comprising: (i) a compound of formula (II), or any embodiment or variation thereof, e.g., a compound of formula (I), (I'), (IA), (IB), (IC), (ID), (IE), (IF), (IG), or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.

[0020] In one aspect, provided herein is a method of modulating APOL1 in a cell, the method comprising exposing the cell to an effective amount of a composition comprising a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. In another variation, provided herein is a method of modulating APOL1 in a cell, comprising exposing the cell to an effective amount of a composition comprising a compound of formula (I'), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I'), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.In another variation, provided herein is a method of modulating APOL1 in a cell, comprising exposing the cell to an effective amount of a composition comprising a compound of formula (II), or any embodiment or variation thereof, such as a compound of formula (I), (I'), (IA), (IB), (IC), (ID), (IE), (IF), (IG), or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (II), or any embodiment or variation thereof, such as a compound of formula (I), (II), (IA), (IB), (IC), (ID), (IE), (IF), (IG), or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.

[0021] In one aspect, provided herein is a method of inhibiting APOL1 in a cell, the method comprising exposing the cell to an effective amount of a composition comprising a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. In another variation, provided herein is a method of inhibiting APOL1 in a cell, comprising exposing the cell to an effective amount of a composition comprising a compound of formula (I'), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.In another variation, provided herein is a method of inhibiting APOL1 in a cell, comprising exposing the cell to an effective amount of a composition comprising a compound of formula (II), or any embodiment or variation thereof, such as a compound of formula (I), (I'), (IA), (IB), (IC), (ID), (IE), (IF), (IG), or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising (i) a compound of formula (II), or any embodiment or variation thereof, such as a compound of formula (I), (I'), (IA), (IB), (IC), (ID), (IE), (IF), (IG), or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.

[0022] In one aspect, provided herein is a method of treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof, the method comprising administering to the individual an effective amount of a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising: (i) a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients. In another variation, provided herein is a method of treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to the individual an effective amount of a compound of formula (I'), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising: (i) a compound of formula (I'), or any embodiment or variation thereof, such as a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.In another variation, provided herein is a method of treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to the individual an effective amount of a compound of formula (II), or any embodiment or variation thereof, such as (I'), (IA), (IB), (IC), (ID), (IE), (IF), (IG), or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising: (i) a compound of formula (II), or any embodiment or variation thereof, such as (I'), (IA), (IB), (IC), (ID), (IE), (IF), (IG), or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.

[0023] In one aspect, provided herein is a kit comprising: (i) a compound of formula (I), or any embodiment or variation thereof, e.g., a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) instructions for use in treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof. In another variation, provided herein is a kit comprising: (i) a compound of formula (I'), or any embodiment or variation thereof, e.g., a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) instructions for use in treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof. In another variation, provided herein is a kit comprising (i) a compound of formula (II), or any embodiment or variation thereof, e.g., a compound of formula (II), (I), (I'), (IA), (IB), (IC), (ID), (IE), (IF), (IG) or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) instructions for use in treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof.

[0024] In some aspects, provided herein are methods of preparing a compound of formula (I), or any embodiment or variation thereof, e.g., a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In another variation, provided herein are methods of preparing a compound of formula (I'), or any embodiment or variation thereof, e.g., a compound of formula (I), (IA), (IB), (IC), (ID), (IE), (IF), or (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In another variation, provided herein is a method of preparing a compound of formula (I'), or any embodiment or variation thereof, e.g., a compound of formula (I), (I'), (IA), (IB), (IC), (ID), (IE), (IF), (IG), or (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. DETAILED DESCRIPTION OF THE INVENTION

[0025] Unless expressly indicated otherwise, the terms "a," "an," etc. refer to one or more.

[0026] As used herein, "about" a parameter or value includes and describes the parameter or value itself. For example, "about X" includes and describes X itself.

[0027] "Individual" refers to a mammal, including humans and non-human mammals. Examples of individuals include, but are not limited to, some primates and humans. In some embodiments, an individual refers to a human.

[0028] As used herein, an "at risk" individual is an individual who is at risk of developing a disease or condition. An "at risk" individual may or may not have detectable disease or condition, and may or may not exhibit detectable disease before the treatment methods described herein. "At risk" refers to the presence of one or more so-called risk factors, which are measurable parameters that correlate with the development of a disease or condition and are known in the art. Individuals who have one or more of these risk factors have a higher likelihood of developing a disease or condition than individuals who do not have these risk factor(s).

[0029] "Treatment" or "treating" is an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired results may include one or more of the following: reducing one or more symptoms caused by a disease or condition; attenuating the severity of a disease or condition; slowing or halting the onset of one or more symptoms associated with a disease or condition (e.g., stabilizing a disease or condition, preventing or delaying the worsening or progression of a disease or condition); and alleviating the disease, such as by causing regression of clinical symptoms (e.g., ameliorating a disease state, improving the effectiveness of another medication, slowing the progression of a disease, improving quality of life, and / or prolonging survival).

[0030] As used herein, "delaying" the onset of a disease or condition means to postpone, prevent, slow, retard, stabilize, and / or postpone the onset of the disease or condition. This delay can be of varying lengths of time, depending on the disease being treated and / or the medical history of the individual. As will be apparent to one of skill in the art, a sufficient or significant delay can, in fact, encompass prevention, in that the individual does not develop the disease or condition.

[0031] As used herein, the term "therapeutically effective amount" or "effective amount" refers to an amount of a compound of the present disclosure or a pharmaceutical salt thereof that is sufficient to achieve treatment when administered to an individual.As understood in the art, an effective amount can be in one or more doses, for example, a single dose or multiple doses may be required to achieve a desired treatment endpoint.An effective amount can be considered in relation to administering one or more therapeutic agents, and a single agent can be considered to be given in an effective amount if, in combination with one or more other agents, a desired or beneficial result can be achieved or is achieved.

[0032] As used herein, "unit dosage form" refers to physically discrete units suitable as unit dosages, each containing a predetermined amount of active ingredient or compound (which may be in a pharmaceutically acceptable carrier).

[0033] As used herein, "pharmaceutically acceptable" means a substance that is not biologically or otherwise undesirable, e.g., the substance can be incorporated into a pharmaceutical composition that is administered to an individual without causing significant undesirable biological effects.

[0034] The term "alkyl," as used herein, refers to an unbranched or branched saturated hydrocarbon chain. As used herein, alkyl refers to an alkyl group having 1 to 20 carbons (i.e., C 1-20 alkyl), 1 to 16 carbons (i.e., C 1-16 alkyl), 1 to 12 carbons (i.e., C 1-12 alkyl), 1 to 10 carbons (i.e., C 1-10 alkyl), 1 to 8 carbons (i.e., C 1-8 alkyl), 1 to 6 carbons (i.e., C 1-6 alkyl), 1 to 4 carbons (i.e., C 1-4 alkyl), or 1 to 3 carbons (i.e., C 1-3alkyl). Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neo-pentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue having a specific number of carbon atoms is named by a chemical name or molecular formula, all positional isomers having that number of carbon atoms are encompassed. For example, "butyl" includes n-butyl, sec-butyl, isobutyl, and tert-butyl; "propyl" includes n-propyl and isopropyl. Certain commonly used alternative names may be used and will be understood by those skilled in the art. For example, a divalent group, such as a divalent "alkyl" group, may be referred to as an "alkylene."

[0035] The term "alkoxy" as used herein refers to an -O-alkyl moiety. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy.

[0036] The term "aryl," as used herein, refers to a fully unsaturated carbocyclic ring moiety. The term "aryl" encompasses monocyclic and polycyclic fused ring moieties. As used herein, aryl refers to, for example, a ring having 6 to 20 ring carbon atoms (i.e., C 6-20 aryl), 6 to 16 ring carbon atoms (i.e., C 6-16 aryl), 6 to 12 ring carbon atoms (i.e., C 6-12 aryl), or 6 to 10 ring carbon atoms (i.e., C 6-10 Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, fluorenyl, and anthryl.

[0037] The term "cycloalkyl," as used herein, refers to a saturated or partially unsaturated carbocyclic ring moiety. The term "cycloalkyl" encompasses monocyclic and polycyclic ring moieties, which may be fused, branched, or spiro. Cycloalkyl includes cycloalkenyl groups, where the ring moiety contains at least one ring double bond. Cycloalkyl includes any polycyclic carbocyclic ring moiety containing at least one non-aromatic ring, regardless of the point of attachment to the rest of the molecule. As used herein, cycloalkyl includes, for example, cycloalkyls having 3 to 20 ring carbon atoms (i.e., C 3-20 cycloalkyl), 3 to 16 ring carbon atoms (i.e., C 3-16 cycloalkyl), 3 to 12 ring carbon atoms (i.e., C 3-12 cycloalkyl), 3 to 10 ring carbon atoms (i.e., C 3-10 cycloalkyl), 3 to 8 ring carbon atoms (i.e., C 3-8 cycloalkyl), 3 to 6 ring carbon atoms (i.e., C 3-6 cycloalkyl), or 3 to 5 ring carbon atoms (i.e., C 3-5 Cycloalkyl includes rings containing cycloalkyl groups. Monocyclic cycloalkyl ring moieties include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic groups include, for example, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl, norvomyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Furthermore, cycloalkyl also includes spirocycloalkyl ring moieties, for example, spiro[2.5]octanyl, spiro[4.5]decanyl, or spiro[5.5]undecanyl.

[0038] The term "halo," as used herein, refers to the atoms occupying Group VIIA of the periodic table and includes fluorine (fluoro), chlorine (chloro), bromine (bromo), and iodine (iodo).

[0039] The term "heteroaryl," as used herein, refers to an aromatic (fully unsaturated) ring moiety containing one or more ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heteroaryl" includes both monocyclic and polycyclic fused ring moieties. As used herein, heteroaryl may contain, for example, 5 to 20 ring atoms (i.e., 5-20-membered heteroaryl), 5 to 16 ring atoms (i.e., 5-16-membered heteroaryl), 5 to 12 ring atoms (i.e., 5-12-membered heteroaryl), 5 to 10 ring atoms (i.e., 5-10-membered heteroaryl), 5 to 8 ring atoms (i.e., 5-8-membered heteroaryl), or 5 to 6 ring atoms (i.e., 5-6-membered heteroaryl). Any monocyclic or polycyclic aromatic ring moiety containing one or more ring heteroatoms is considered heteroaryl, regardless of the point of attachment to the remainder of the molecule (i.e., the heteroaryl moiety can be attached to the remainder of the molecule through any ring carbon or any ring heteroatom of the heteroaryl moiety). Examples of heteroaryl groups include acridinyl, benzimidazolyl, benzindolyl, benzofuranyl, benzonaphthofuranyl, benzoxazolyl, benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridyl, carbazolyl, dibenzofuranyl, dibenzothiophenyl, furanyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, isoquinolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, and the like. Examples of fused heteroaryl rings include, but are not limited to, aryl, oxazolyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, phenazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, triazolyl, tetrazolyl, and triazinyl. Examples of fused heteroaryl rings include, but are not limited to, quinolinyl, isoquinolinyl, benzo[b]thiophenyl, indazolyl, benzo[d]imidazolyl, pyrazolo[1,5-a]pyridinyl, and imidazo[1,5-a]pyridinyl, where the heteroaryl may be attached via either ring of the fused system.

[0040] The term "heterocyclyl," as used herein, refers to a saturated or partially unsaturated cyclic moiety containing one or more ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heterocyclyl" includes both monocyclic and polycyclic ring moieties (polycyclic ring moieties can be fused, bridged, or spiro). Any non-aromatic monocyclic or polycyclic ring moiety containing at least one ring heteroatom is considered heterocyclyl, regardless of the point of attachment to the rest of the molecule (i.e., the heterocyclyl moiety can be attached to the rest of the molecule through any ring carbon or any ring heteroatom of the heterocyclyl moiety). Furthermore, the term heterocyclyl is intended to encompass any polycyclic ring moiety containing at least one ring heteroatom, where the polycyclic ring moiety contains at least one non-aromatic ring, regardless of the point of attachment to the rest of the molecule. As used herein, heterocyclyl includes, for example, 3 to 20 ring atoms (i.e., 3-20-membered heterocyclyl), 3 to 16 ring atoms (i.e., 3-16-membered heterocyclyl), 3 to 12 ring atoms (i.e., 3-12-membered heterocyclyl), 3 to 10 ring atoms (i.e., 3-10-membered heterocyclyl), 3 to 8 ring atoms (i.e., 3-8-membered heterocyclyl), 3 to 6 ring atoms (i.e., 3-6-membered heterocyclyl), 3 to 5 ring atoms (i.e., 3-5-membered heterocyclyl), 5 to 8 ring atoms (i.e., 5-8-membered heterocyclyl), or 5 to 6 ring atoms (i.e., 5-6-membered heterocyclyl).Examples of heterocyclyl groups include, for example, azetidinyl, azepinyl, benzodioxolyl, benzo[b][l,4]dioxepinyl, 1,4-benzodioxanyl, benzopyranyl, benzodioxinyl, benzopyranonyl, benzofuranonyl, dioxolanyl, dihydropyranyl, hydropyranyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, furanonyl, imidazolinyl, imidazolidinyl, indolinyl, indolizinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoquinolyl, and the like. These include thioindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, oxiranyl, oxetanyl, phenothiazinyl, phenoxazinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tetrahydropyranyl, trithianyl, tetrahydroquinolinyl, thiophenyl (i.e., thienyl), thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Examples of spiroheterocyclyl rings include, but are not limited to, bicyclic and tricyclic ring systems such as oxabicyclo[2.2.2]octanyl, 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, and 6-oxa-1-azaspiro[3.3]heptanyl. Examples of fused heterocyclyl rings include, but are not limited to, 1,2,3,4-tetrahydroisoquinolinyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridinyl, indolinyl, and isoindolinyl, where the heterocyclyl may be attached via either ring of the fused system.

[0041] The terms "any" and "optionally," as used herein, mean that the subsequently described event or circumstance may or may not occur, and that the description includes cases where the event or circumstance occurs and cases where it does not. Thus, the term "optionally substituted" implies that any one or more (e.g., 1, 2, 1 to 5, 1 to 3, 1 to 2, etc.) hydrogen atoms on the specified atom or moiety or group may or may not be replaced by a non-hydrogen atom or moiety or group. By way of example and not limitation, the phrase "methyl optionally substituted with one or more chloro" encompasses -CH, -CHCl, -CHCl, and -CCl moieties.

[0042] Aspects and embodiments described herein as "comprising" are understood to include "consisting of" and "consisting essentially of" embodiments.

[0043] As used herein, the term "pharmaceutically acceptable salt" of a given compound refers to a salt that retains the biological effectiveness and properties of the given compound and is not biologically or otherwise undesirable. "Pharmaceutically acceptable salts" include, for example, salts with inorganic acids and salts with organic acids. Also, when a compound described herein is obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid salt. Conversely, when the product is a free base, an addition salt, particularly a pharmaceutically acceptable addition salt, can be produced by dissolving the free base in a suitable organic solvent and treating the solution with an acid according to conventional procedures for preparing acid addition salts from base compounds. Such compositions are well known in the pharmaceutical arts. See, for example, "Handbook of Pharmaceutical Salts Properties, Selection, and Use," International Union of Pure and Applied Chemistry, John Wiley & Sons (2008) (incorporated herein by reference). Those skilled in the art will recognize various synthetic methodologies that can be used to prepare non-toxic pharmaceutically acceptable addition salts. Pharmaceutically acceptable acid addition salts can be prepared from inorganic or organic acids. Salts derived from inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. Salts derived from organic acids include, for example, acetic acid, propionic acid, gluconic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, trifluoroacetic acid, etc. Similarly, pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include, by way of example only, sodium, potassium, lithium, aluminum, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines.Specific examples of suitable amines include, by way of example only, isopropylamine, trimethylamine, diethylamine, tri(iso-propyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, and the like.

[0044] Isotopically labeled forms of the compounds described herein can be prepared.Isotopically labeled compounds have the structure described herein, except that one or more atoms are replaced by atoms with a selected atomic mass or mass number.Examples of isotopes that can be incorporated into the disclosed compounds include hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, for example, 2 H, 3 H, 11 C. 13 C. 14 C. 13 N, 15 N, 15 O. 17 O. 18 O. 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 Included are isotopes of I. In some embodiments, compounds of Formula (I) or Formula (I') are provided wherein one or more hydrogens have been replaced with deuterium or tritium.

[0045] Some of the compounds provided herein may exist as tautomers. Tautomers are in equilibrium with each other. By way of example, an amide-containing compound may exist in equilibrium with an imidic acid tautomer. Regardless of which tautomer is depicted and the nature of the equilibrium between the tautomers, it will be understood by those skilled in the art that the compounds of the present disclosure include both amide and imidic acid tautomers. Thus, for example, amide-containing compounds are understood to include their imidic acid tautomers. Similarly, imidic acid-containing compounds are understood to include their amide tautomers.

[0046] Also provided herein are prodrugs of the compounds described herein or their pharmaceutically acceptable salts. Prodrugs are compounds that can be administered to an individual and release the compounds described herein as parent drug compounds in vivo. It is understood that prodrugs can be prepared by modifying functional groups on the parent drug compound so that the modifications are cleaved in vivo to release the parent drug compound. The development of prodrug compounds is well known in the pharmaceutical field. See, for example, Rautio, J., Kumpulainen, H., Heimbach, T. et al. Prodrugs: design and clinical applications. Nat. Rev. Drug. Discov. 7, 255-270 (2008) (incorporated herein by reference).

[0047] The compounds of the present disclosure, or their pharmaceutically acceptable salts, may contain asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined in terms of absolute stereochemistry as (R)- or (S)- (or for amino acids as (D)- or (L)-). The present disclosure is meant to include all such possible isomers, as well as their racemic and optically pure forms and mixtures thereof in any ratio. Optically active (+)- and (−), (R)- and (S)-, or (D)- and (L)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques, such as chromatography and / or fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of the racemate (or racemate of a salt or derivative) using, for example, chiral high-pressure liquid chromatography (HPLC) or chiral supercritical fluid chromatography (SFC). Where the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, unless otherwise specified, the disclosure is intended to include both E and Z geometric isomers. Similarly, cis- and trans- are used in their conventional sense to describe their relative spatial relationships.

[0048] "Stereoisomers" refer to compounds composed of the same atoms bonded by the same bonds but with different, non-interchangeable three-dimensional structures. The present disclosure contemplates various stereoisomers, or mixtures thereof, including "enantiomers," which refer to two stereoisomers whose structures are non-superimposable mirror images of each other. "Diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other.

[0049] Where enantiomeric and / or diastereomeric forms of a given structure exist, a planar bond indicates that all stereoisomeric forms of the shown structure may be present. For example, [ka]

[0050] Where enantiomeric forms of a given structure exist, the presence of a flat bond and "*" symbol indicates that the composition consists of at least 90% by weight of a single isomer of the unknown absolute stereochemistry. For example, [ka]

[0051] Where enantiomeric and / or diastereomeric forms of a given structure exist having more than one stereocenter, the presence of a flat bond and more than one "*" symbol indicates that the composition is made up of at least 90% by weight of a single enantiomer or diastereomer of the unknown absolute stereochemistry. For example, [ka]

[0052] Where enantiomeric and / or diastereomeric forms of a given structure exist, the composition is comprised of at least 90% by weight, and a dash or V designates a single enantiomer or diastereomer of known relative or absolute stereochemistry. For example, [ka]

[0053] The abbreviations used are conventional in the art and are taken from the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 th Ed, which is incorporated herein by reference in its entirety. The following examples are intended to be illustrative only and not limiting in any way. [Table 65-1] [Table 65-2]

[0054] compound As used herein, a compound of formula (II): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 If present, each occurrence independently represents halo, -CN, C 1-6 Alkoxy, and C 1-6 is selected from the group consisting of alkyl, R 1 C 1-6 the alkoxy is optionally substituted with one or more halo; R 1 C 1-6 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-6 Alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; R 2 C 1-6 Alkyl is a group consisting of one or more deuterium, halo, -OH, -NH2, or C 1-6 optionally substituted with alkoxy; R 2 C 3-10 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-6 is alkyl; L 1 is C 1-6 is alkylene, L 1 C 1-6 Alkylene is a group consisting of one or more deuterium or C 1-6 optionally substituted with alkyl; C1-6 Alkyl is one or more -OH or C 1-6 optionally further substituted with alkoxy; L 2 is O or N(R x ) and R x is H or C 1-6 is alkyl; (1)L 3 is absent or O, C 3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 is alkylene, L 3 C 3-10 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; L 3 C 1-6 Alkylene is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; C 1-6 The alkyl is optionally substituted with one or more -OH; L 3 3-10 membered heterocyclyl is one or more -OH or C 1-6 optionally substituted with alkyl; X 1 and X 2 are each independently N or C(R 5 ) and; R 4 teeth, (i)-S(O)2-R a ; (ii) 5- to 20-membered heteroaryl, where R 4 The 5- to 20-membered heteroaryl may have one or more C 1-6 optionally substituted with alkyl; (iii)-N(R d )2, and R d is independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-6alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-6 alkyl)2, and C 1-6 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-6 alkyl, or a 3- to 10-membered heterocycle; R e is optionally substituted with one or more oxo, or both R e together with the N to which they are attached form a 3- to 10-membered heterocyclyl; 3- to 10-membered heterocyclyl may be one or more of halo, oxo, -OH, NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-6 Alkyl, -OH, oxo or -S(O)R a 3- to 10-membered heterocyclyl optionally substituted with (vii)-S(O)-N(C 1-6 alkyl)-(C 1-6 alkyl), (viii)-CN, (ix)-(CH2) q OH, where q is an integer from 0 to 6; (x)-C(O)-C 1-6 alkyl, or (xi)-P(O)(C 1-6 alkyl)2; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4and N or C, which together with the atom to which they are attached form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b is optionally replaced by R b is independently, at each occurrence, -OH, halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl can be one or more of halo, OH, -S(O)2-C 1-6 Alkyl, or C 3-10 optionally substituted with cycloalkyl; R b C 1-6 Alkyl C 3-10 Cycloalkyl is one or more C 1-6 optionally further substituted with alkyl or —OH; R b C 3-10 Cycloalkyl is a group consisting of one or more -OH, C 3-10 Cycloalkyl, or C 1-6 optionally substituted with alkyl; R b C 3-10 Cycloalkyl C 1-6 the alkyl is optionally further substituted with one or more -OH, deuterium, or halo; A 5- to 20-membered heteroaryl may have one or more R c is optionally replaced by R c is independently present in each occurrence, halo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R c C 1-6 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl; R c C 3-10 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; R c 3-10 membered heterocyclyl is one or more -OH or C 1-6 optionally substituted with alkyl; R c 3- to 10-membered heterocyclyl C 1-6 The alkyl is optionally further substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 C optionally substituted with alkyl 1-6 Alkyl, (ii) one or more -OH, -C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, or -C(O)-C 3-10 Heterocyclyl, or C 1-6 C optionally substituted with alkyl 3-10 cycloalkyl, C 1-6 alkyl optionally substituted with one or more -OH; (iii) one or more C 1-6 a 3- to 10-membered heterocyclyl optionally substituted with alkyl, or (iv) NH(C 1-6 alkyl); R 5 is independently, at each occurrence, H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is an alkoxy; R 5 C 1-6 the alkyl is optionally substituted with one or more halo or -OH; R 5 C 1-6 The alkoxy is optionally substituted with one or more halo; X 3 is N or C(R 6 ) and; X 4 is N or C(R 7 ) and; R 6 and R 7 are each independently H or halo. is provided.

[0055] As used herein, a compound of formula (I'): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 If present, each occurrence independently represents halo, -CN, C 1-6 Alkoxy, or C 1-6 is selected from the group consisting of alkyl, R 1 C 1-6 the alkoxy is optionally substituted with one or more halo; R 1 C 1-6 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-6 Alkyl, C 3-10cycloalkyl, or 3- to 15-membered heterocyclyl; R 2 C 1-6 Alkyl is one or more of halo, -OH, -NH2, or C 1-6 optionally substituted with alkoxy; R 2 C 3-10 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-6 is alkyl; L 1 is C 1-6 alkylene, and L 1 C 1-6 Alkylene is one or more C 1-6 optionally substituted with alkyl, C 1-6 Alkyl is one or more -OH or C 1-6 optionally further substituted with alkoxy; L 2 is O or N(R x ) and R x is H or C 1-6 is alkyl; (1)L 3 is absent or O, C 3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 is alkylene, C 3-10 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; L 3 C 1-6 Alkylene is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; The 3- to 10-membered heterocyclyl is optionally substituted with one or more -OH; X 1 and X 2 are each independently N or C(R 5 ) and; R 4 teeth, (i)-S(O)2-R a; (ii) 5- to 20-membered heteroaryl, where R 4 The 5- to 20-membered heteroaryl may have one or more C 1-6 optionally substituted with alkyl; (iii)-N(R d )2, and R d is independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-6 alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-6 alkyl)2, and C 1-6 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-6 alkyl, a 3- to 10-membered heterocycle, the 3- to 10-membered heterocycle being optionally substituted with one or more oxo, or both R e together with the N to which they are attached to form a 3- to 10-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-6 Alkyl, -OH, oxo or -S(O)R a 3- to 10-membered heterocyclyl optionally substituted with (vii)-S(O)-N(C 1-6 alkyl)-(C 1-6 alkyl), (viii)-CN, (ix)-(CH2) q OH, where q is an integer from 0 to 6; (x)-C(O)-C 1-6 alkyl, or (xi)-P(O)(C 1-6 alkyl)2; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b optionally substituted with R b is, independently at each occurrence, halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl can be one or more of halo, OH, -S(O)2-C 1-6 Alkyl, or C 3-10 optionally substituted with cycloalkyl; R b C 1-6 Alkyl C 3-10 Cycloalkyl is one or more C 1-6 optionally further substituted with alkyl or —OH; R b C 3-10 Cycloalkyl is a group consisting of one or more -OH, C 3-10 Cycloalkyl, or C 1-6 optionally substituted with alkyl; R b C 3-10 Cycloalkyl C 1-6 The alkyl is optionally further substituted with one or more -OH; A 5- to 20-membered heteroaryl may have one or more R c optionally substituted with Rc is independently present in each occurrence, halo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R c C 1-6 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl; R c C 3-10 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; R c 3-10 membered heterocyclyl is one or more -OH or C 1-6 optionally substituted with alkyl; R c 3- to 10-membered heterocyclyl C 1-6 The alkyl is optionally further substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 C optionally substituted with alkyl 1-6 Alkyl, (ii) one or more -OH, -C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, or -C(O)-C 3-10 Heterocyclyl, or C 1-6 C optionally substituted with alkyl 3-10 Cycloalkyl, C 1-6 Alkyl is optionally substituted with one or more -OH, or (iii) one or more C 1-6 a 3- to 10-membered heterocyclyl optionally substituted with alkyl; R 5 is independently, at each occurrence, H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH, and R 5 C 1-6 The alkoxy is optionally substituted with one or more halo; R 6 and R 7 are each independently H or halo. is provided.

[0056] As used herein, compounds of formula (I): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 If present, each occurrence independently represents halo, -CN, C 1-6 Alkoxy or -C 1-6 is selected from the group consisting of alkyl, R 1 C 1-6 the alkoxy is optionally substituted with one or more halo; R 1 C 1-6 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-6 Alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; R 2 C 1-6Alkyl is one or more of halo, -OH, -NH2, or C 1-6 optionally substituted with alkoxy; R 2 C 3-10 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-6 is alkyl; L 1 is C 1-6 alkylene, and L 1 C 1-6 Alkylene is one or more C 1-6 optionally substituted with alkyl, C 1-6 Alkyl is one or more -OH or C 1-6 optionally further substituted with alkoxy; L 2 is O or N(R x ) and R x is H or C 1-6 is alkyl; (1)L 3 is absent or O, C 3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 is alkylene, L 3 C 1-6 Alkylene is one or more C 1-6 optionally substituted with alkyl; The 3- to 10-membered heterocyclyl is optionally substituted with one or more -OH; X 1 and X 2 are each independently N or C(R 5 ) and; R4 is (i)-S(O)2-R a , (ii) 5- to 20-membered heteroaryl, where R 4 The 5- to 20-membered heteroaryl may have one or more C 1-6 optionally substituted alkyl; (iii)-N(R d )2, and R dis independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-6 alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-6 alkyl)2, where R d C 1-6 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-6 alkyl, a 3- to 10-membered heterocycle, the 3- to 10-membered heterocycle being optionally substituted with one or more oxo, or both R e together with the N to which they are attached to form a 3- to 10-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-6 3- to 10-membered heterocyclyl optionally substituted with alkyl or oxo; (vii)-S(O)-N(C 1-6 alkyl)-(C 1-6 alkyl), or (viii) -CN; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b optionally substituted with R bis, independently at each occurrence, halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl is one or more halo, OH, or -S(O)2-C 1-6 optionally substituted with alkyl; R b C 3-10 cycloalkyl is optionally substituted with one or more -OH; A 5- to 20-membered heteroaryl may have one or more R c optionally substituted with R c is independently present in each occurrence, halo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 selected from the group consisting of cycloalkyl, and 3- to 10-membered heterocyclyl; R c C 1-6 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl; R c C 3-10 The cycloalkyl is optionally substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 C optionally substituted with alkyl 1-6 alkyl, or (ii) one or more -OH, -C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, or -C(O)-C 3-10 Heterocyclyl, or C 1-6 C optionally substituted with alkyl 3-10 Cycloalkyl, C 1-6 Alkyl is optionally substituted with one or more -OH, or (iii) one or more C 1-6 a 3- to 10-membered heterocyclyl optionally substituted with alkyl; R 5 is independently, at each occurrence, H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or -OH, and 1-6 The alkoxy is optionally substituted with one or more halo; R 6 and R 7 are each independently H or halo. is provided.

[0057] Any embodiment provided herein of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, is also an embodiment of a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0058] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is an integer from 0 to 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0059] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is H, C 1-6 Alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl, and R 2 C 1-6 Alkyl is one or more of halo, -OH, -NH2, or C 1-6 optionally substituted with alkoxy, R 2 C 3-10 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R 2 is H, C 1-3 Alkyl, C 3-6 cycloalkyl, or 3- to 6-membered heterocyclyl, and R 2 C 1-3 Alkyl is one or more of halo, -OH, -NH2, or C 1-3 optionally substituted with alkoxy, R 2 C 3-6 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R 2 H, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0060] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is H, C 1-6 Alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl, and R 2 C 1-6 Alkyl is a group consisting of one or more deuterium, halo, -OH, -NH2, or C 1-6 optionally substituted with alkoxy, R 2 C 3-10 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R 2 is H, C 1-3 Alkyl, C 3-6 cycloalkyl, or 3- to 6-membered heterocyclyl, and R 2 C 1-3 Alkyl is a group consisting of one or more deuterium, halo, -OH, -NH2, or C 1-3 optionally substituted with alkoxy, R 2 C 3-6 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R 2 H, [ka] is selected from the group consisting of:

[0061] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0062] In some embodiments of a compound of Formula (I), Formula (I′), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 In some embodiments, R 2 is C 1-3 In some embodiments, R 2 is methyl or ethyl. In some embodiments, R 2 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0063] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is one or more halo, -OH, -NH2, or C 1-6 C optionally substituted with alkoxy 1-6 In some embodiments, R 2 is one or more halo, -OH, -NH2, or C 1-3 C optionally substituted with alkoxy 1-3 In some embodiments, R 2 is methyl. In some embodiments, R 2 is one or more halo, -OH, -NH2, or C 1-6 In some embodiments, R is ethyl optionally substituted with alkoxy. 2 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0064] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is one or more deuterium, halo, -OH, -NH2, or C 1-6 C optionally substituted with alkoxy 1-6 In some embodiments, R 2 is one or more deuterium, halo, -OH, -NH2, or C 1-3 C optionally substituted with alkoxy 1-3 In some embodiments, R 2 is methyl. In some embodiments, R 2 is one or more halo, -OH, -NH2, or C 1-6 In some embodiments, R is ethyl optionally substituted with alkoxy. 2 teeth, [ka] is selected from the group consisting of:

[0065] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 3-10 is cycloalkyl, and R 2 C 3-10 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R 2 is C 3-6 is cycloalkyl, and R 2 C 3-6The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R 2 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0066] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is a 3- to 15-membered heterocyclyl. In some embodiments, R 2 is a 3- to 6-membered heterocyclyl. In some embodiments, R 2 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0067] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0068] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 Halo, -CN, C 1-6 Alkoxy or -C 1-6 alkyl, C 1-6 Alkoxy or R 1 is optionally substituted with one or more halo, and R 1 C 1-6 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 Halo, -CN, C 1-3 Alkoxy, or -C 1-3 alkyl, and R 1 C 1-3 The alkoxy is optionally substituted with one or more halo, and R 1 C 1-3 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is Cl, Br, -CN, methyl, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0069] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 Halo, -CN, C 1-6 Alkoxy or -C 1-6 alkyl, C 1-6 Alkoxy or R 1 is optionally substituted with one or more halo, and R 1 C 1-6 The alkyl is optionally substituted with one or more halo. In some embodiments, R1 Halo, -CN, C 1-3 Alkoxy, or -C 1-3 alkyl, and R 1 C 1-3 The alkoxy is optionally substituted with one or more halo, and R 1 C 1-3 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 are Cl, Br, F, I, -CN, methyl, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0070] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some embodiments, R 1 is Br. In some embodiments, R 1 is F. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0071] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some embodiments, R 1 is Br. In some embodiments, R 1is F. In some embodiments, R 1 is I. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0072] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is C 1-6 alkyl, and R 1 C 1-6 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is C 1-3 alkyl, and R 1 C 1-3 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is C 1-3 alkyl, and R 1 C 1-3 The alkyl is optionally substituted with one or more F. In some embodiments, R 1 is methyl and R 1 The methyl in R is optionally substituted with one or more F. In some embodiments, R 1 is methyl. In some embodiments, R 1 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0073] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1 is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0074] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is C 1-6 is alkoxy, and R 1 C 1-6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 1 is C 1-3 is alkoxy, and R 1 C 1-3 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 1 is C 1-3 is alkoxy, and R 1 C 1-3 The alkoxy is optionally substituted with one or more F. In some embodiments, R 1 is methoxy and R 1 The methoxy in R is optionally substituted with one or more F. In some embodiments, R 1 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0075] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, p is an integer from 0 to 10. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0076] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 3 is C 1-6 In some embodiments, R 3 is C 1-3 In some embodiments, R 3 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0077] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (R 1 ) m and R 2is a 2-indolinone optionally substituted at one or more of positions 1, 5, and 7. In some embodiments, the 2-indolinone ring is unsubstituted. In some embodiments, the 2-indolinone ring is substituted at position 1. In some embodiments, the 2-indolinone ring is substituted at position 5. In some embodiments, the 2-indolinone ring is substituted at position 7. In some embodiments, the 2-indolinone ring is substituted at positions 1 and 5. In some embodiments, the 2-indolinone ring is substituted at positions 5 and 7. In some embodiments, the 2-indolinone ring is substituted at positions 1, 5, and 7. In some embodiments, positions 1, 5, and 7 are substituted with the structure [ka] where position 1 is an N atom, positions 5 and 7 are each a C atom, and ## represents the point of attachment to the remainder of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0078] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (R 1 ) m and R 2 The rings that possess [ka] and ## represents the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0079] In some embodiments of the compounds of Formula (I), Formula (I′), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (R 1 ) m and R 2 The rings that possess [ka] and ## represents the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0080] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (R 1 ) m and R 2 The rings that possess [ka] where ## represents the point of attachment to the rest of the molecule.

[0081] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (R 3 ) p The rings that possess [ka] and ## represents the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0082] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0083] In some embodiments of the compounds of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0084] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] In some embodiments, (R 1 ) m , R 2 , and (R 3 ) p The rings that possess [ka] is.

[0085] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is one or more C 1-6 C optionally substituted with alkyl 1-6 alkylene, C 1-6 Alkyl is -OH or C 1-6 In some embodiments, L is optionally substituted with alkoxy. 1 is one or more C 1-3 C optionally substituted with alkyl 1-3 alkylene, C 1-3 Alkyl is -OH or C 1-3 In some embodiments, L is optionally substituted with alkoxy. 1 is methylene. In some embodiments, L 1is ethylene. In some embodiments, L 1 is one or more C 1-3 ethylene optionally substituted with alkyl, C 1-3 Alkyl is one or more -OH or C 1-3 In some embodiments, L is optionally substituted with alkoxy. 1 teeth, [ka] and each L is selected from the group consisting of 1 About #, L 2 indicates the point of attachment to the remainder of the molecule, and ## indicates the point of attachment to the remainder of the molecule. In some variations, the embodiments provided herein also apply to compounds of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0086] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is one or more deuterium atoms, or C 1-6 C optionally substituted with alkyl 1-6 alkylene, C 1-6 Alkyl is -OH or C 1-6 In some embodiments, L is optionally substituted with alkoxy. 1 is one or more deuterium atoms, or C 1-3 C optionally substituted with alkyl 1-3 alkylene, C 1-3 Alkyl is -OH or C 1-3 In some embodiments, L is optionally substituted with alkoxy. 1 is methylene. In some embodiments, L 1 is ethylene. In some embodiments, L 1 is one or more deuterium atoms, or C 1-3 ethylene optionally substituted with alkyl, C 1-3Alkyl is one or more -OH or C 1-3 In some embodiments, L is optionally substituted with alkoxy. 1 teeth, [ka] and each L is selected from the group consisting of 1 About #, L 2 indicates the point of attachment to the remainder of the molecule, and ## indicates the point of attachment to the remainder of the molecule.

[0087] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 2 is O or N(R x ) and R x is H or C 1-6 In some embodiments, L 2 is O or N(R x ) and R x is H or C 1-3 In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0088] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 2 is O. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0089] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent or O, C3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 alkylene, and L 3 C 1-6 Alkylene is one or more C 1-6 optionally substituted with alkyl; 3 C 3-10 Cycloalkyl is optionally substituted with one or more -OH groups, and L 3 The 3- to 10-membered heterocyclyl is optionally substituted with one or more —OH. 3 non-existent, or O, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0090] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent or O, C 3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 alkylene, C 3-10 Cycloalkyl is a group consisting of one or more -OH, or C 1-6 optionally substituted with alkyl; 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 In some embodiments, L is optionally substituted with alkyl, and 3- to 10-membered heterocyclyl is optionally substituted with one or more —OH. 3 is non-existent, or O, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0091] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent or O, C 3-10 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 alkylene, and L 3 C 3-10 Cycloalkyl is a group consisting of one or more -OH, or C 1-6 optionally substituted with alkyl; L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 optionally substituted with alkyl, C 1-6 Alkyl is optionally substituted with one or more -OH; 3- to 10-membered heterocyclyl is optionally substituted with one or more -OH or C 1-6 In some embodiments, L is optionally substituted with alkyl. 3 is non-existent, or O, [ka] is selected from the group consisting of:

[0092] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0093] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is O. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0094] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 In some embodiments, L is alkylene. 3 is C 1-3 In some embodiments, L is alkylene. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0095] In some embodiments of the compounds of Formula (I), Formula (I′), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 In some embodiments, L is optionally substituted with alkyl. 3 is C 1-3 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6In some embodiments, L is optionally substituted with alkyl. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0096] In some embodiments of the compound of Formula (II) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 optionally substituted with alkyl, C 1-6 The alkyl is optionally substituted with one or more —OH. In some embodiments, L 3 is C 1-3 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 In some embodiments, L is optionally substituted with alkyl. 3 teeth, [ka] is selected from the group consisting of:

[0097] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 3-10 is cycloalkyl, and L 3 C 3-10 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 is C3-8 is cycloalkyl, and L 3 C 3-8 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0098] In some embodiments of a compound of Formula (I'), (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 3-10 is cycloalkyl, and L 3 C 3-10 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 is C 3-8 is cycloalkyl, and L 3 C 3-8 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0099] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3 is 3-10 membered heterocyclyl. In some embodiments, L 3 is a 3- to 6-membered heterocyclyl. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0100] In some embodiments of a compound of Formula (I), Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3 is a 3- to 10-membered heterocyclyl. 3 is 3-6 membered heterocyclyl. In some embodiments, L3 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0101] In some embodiments of a compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L3 is a 3- to 10-membered heterocyclyl. 3 is 3-6 membered heterocyclyl. In some embodiments, L3 is [ka] is selected from the group consisting of:

[0102] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a , 5-20 membered heteroaryl, -N(R d )2, -NS(O)-(C 1-6 alkyl)2, -C(O)-N(R e ) 2, 3 to 10-membered heterocyclyl, -S(O)(NC 1-6 alkyl)-(C 1-6 alkyl), or -CN. In some embodiments, R 4 is S(O)2-R a , 5-10 membered heteroaryl, -N(R d )2, -NS(O)-(C 1-3 alkyl)2, -C(O)-N(R e ) 2, 3 to 6-membered heterocyclyl, -S(O)(NC 1-3 alkyl)-(C 1-3 alkyl), or -CN. In some embodiments, R 4 is -NH2, -CN, -C(O)-N(CH3)2, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0103] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a , 5-20 membered heteroaryl, -N(R d )2, -NS(O)-(C 1-6 alkyl)2, -C(O)-N(R e ) 2, 3 to 10-membered heterocyclyl, -S(O)-N(C 1-6 alkyl)-(C1-6 alkyl), -CN, -(CH2) q OH, -C(O)-C 1-6 Alkyl, or -P(O)(C 1-6 In some embodiments, R 4 is S(O)2-R a , 5-10 membered heteroaryl, -N(R d )2, -NS(O)-(C 1-3 alkyl)2, -C(O)-N(R e ) 2, 3 to 6-membered heterocyclyl, -S(O)(NC 1-3 alkyl)-(C 1-3 alkyl), -CN, -OH, -CHOH, -C(O)-C 1-3 Alkyl, or -P(O)(C 1-3 In some embodiments, R 4 is -NH2, -CN, -OH, -CH2OH, -C(O)-N(CH3)2, [ka] is selected from the group consisting of:

[0104] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is one or more halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 C optionally substituted with alkyl 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is one or more halo, -OH, -S(O)2-C 1-3 Alkyl, or -N(C1-3 alkyl)-C(O)-C 1-3 C optionally substituted with alkyl 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0105] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is one or more halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 C optionally substituted with alkyl 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is one or more halo, -OH, -S(O)2-C 1-3 Alkyl, or -N(C 1-3 alkyl)-C(O)-C 1-3 C optionally substituted with alkyl 1-3 In some embodiments, R 4 teeth, [ka] is selected from the group consisting of:

[0106] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 3-10 In some embodiments, R 4 is -S(O)2-R a and R a is one or more -OH, C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -C(O)-C 3-10 Heterocyclyl or C 1-6 C optionally substituted with alkyl 3-10 is cycloalkyl, C 1-6 The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 is -S(O)2-R a and R a is one or more -OH, C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -C(O)-C 3-10 Heterocyclyl, or C 1-6 C optionally substituted with alkyl 3-6 is cycloalkyl, C 1-6 The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 is -S(O)2-R a and R a is one or more -OH, C(O)2-C 1-3 Alkyl, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -C(O)-C 3-6 Heterocyclyl, or C 1-3 C optionally substituted with alkyl 3-6 is cycloalkyl, C 1-3The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0107] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is a 3- to 10-membered heterocyclyl. In some embodiments, R 4 is -S(O)2-R a and R a is one or more C 1-6 In some embodiments, R is a 3- to 10-membered heterocyclyl optionally substituted with alkyl. 4 is -S(O)2-R a and R a is one or more C 1-6 In some embodiments, R is a 3- to 6-membered heterocyclyl optionally substituted with alkyl. 4 is -S(O)2-R a and R a is one or more C 1-3 In some embodiments, R is a 3- to 6-membered heterocyclyl optionally substituted with alkyl. 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0108] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is a 5- to 20-membered heteroaryl. In some embodiments, R 4 is one or more C 1-6 In some embodiments, R is a 5- to 20-membered heteroaryl optionally substituted with alkyl. 4 is one or more C 1-6 In some embodiments, R is a 5- to 6-membered heteroaryl optionally substituted with alkyl. 4 is one or more C 1-3 In some embodiments, R is a 5- to 6-membered heteroaryl optionally substituted with alkyl. 4 is a 5-6 membered heteroaryl optionally substituted with one or more methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0109] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R dC 1-6 Alkyl is optionally substituted with one or more -OH, and R a is C 1-6 In some embodiments, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R d C 1-3 Alkyl is optionally substituted with one or more -OH, and R a is C 1-3 In some embodiments, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R d C 1-3 Alkyl is optionally substituted with one or more -OH, and R a is methyl. In some embodiments, R 4 is -NH2, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0110] In some embodiments of a compound of Formula (I), Formula (I′), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R d C 1-6 Alkyl is optionally substituted with one or more -OH, and R a is C1-6 In some embodiments, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R d C 1-3 Alkyl is optionally substituted with one or more -OH, and R a is C 1-3 In some embodiments, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R d C 1-3 Alkyl is optionally substituted with one or more -OH, and R a is methyl. In some embodiments, R 4 is -NH2, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0111] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2 and R e each independently represents H or C 1-6 In some embodiments, R 4 is -C(O)-N(R e )2 and R e each independently represents H or C 1-3 In some embodiments, R 4 is -C(O)-N(R e)2 and R e Each of R is independently H or methyl. 4 is —C(O)—NH. In some embodiments, R 4 is —C(O)—NH(CH). In some embodiments, R 4 is —C(O)—N(CH) 2. In some variations, the embodiments provided herein also apply to compounds of formula (I′), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0112] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2 and R e is independently H or a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more oxo. 4 is -C(O)-N(R e )2 and R e is independently H or a 3- to 6-membered heterocycle, wherein the 3- to 6-membered heterocycle is optionally substituted with one or more oxo. 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0113] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(Re )2, and both R e together with the N to which they are attached form a 3- to 10-membered heterocyclyl. In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached to form a 3- to 10-membered heterocyclyl, which may be one or more of halo, oxo, -OH, -NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with R a is C 1-6 In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached to form a 3- to 7-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, NH-S(O)-R a , or -S(O)2-R a optionally substituted with R a is C 1-3 In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached to form a 3- to 7-membered heterocyclyl, which may be one or more of halo, oxo, -OH, -NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with R a is methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0114] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is one or more oxo or C 1-6 In some embodiments, R is a 3- to 10-membered heterocyclyl optionally substituted with alkyl. 4 is one or more oxo or C 1-6 In some embodiments, R is a 3- to 7-membered heterocyclyl optionally substituted with alkyl. 4 is one or more oxo or C 1-3 In some embodiments, R is a 3- to 7-membered heterocyclyl optionally substituted with alkyl. 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0115] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is one or more C 1-6 Alkyl, -OH, oxo or -S(O)R a In some embodiments, R is a 3- to 10-membered heterocyclyl optionally substituted with 4 is one or more C 1-6 Alkyl, -OH, oxo or -S(O)R aIn some embodiments, R 4 is one or more C 1-3 Alkyl, -OH, oxo or -S(O)R a In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0116] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is one or more C 1-6 Alkyl, -OH, oxo or -S(O)R a In some embodiments, R is a 3- to 10-membered heterocyclyl optionally substituted with 4 is one or more C 1-6 Alkyl, -OH, oxo or -S(O)R a In some embodiments, R 4 is one or more C 1-3 Alkyl, -OH, oxo or -S(O)R a In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0117] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is one or more C 1-6 Alkyl, -OH, oxo or -S(O)R a In some embodiments, R is a 3- to 10-membered heterocyclyl optionally substituted with 4 is one or more C 1-6 Alkyl, -OH, oxo or -S(O)R a In some embodiments, R 4 is one or more C 1-3 Alkyl, -OH, oxo or -S(O)R a In some embodiments, R 4 teeth, [ka] is selected from the group consisting of:

[0118] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -NS(O)-(C 1-6 In some embodiments, R 4 is -NS(O)-(C 1-3 In some embodiments, R 4 teeth, [ka] is.

[0119] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)(NC 1-6 alkyl)-(C 1-6In some embodiments, R 4 is -S(O)(NC 1-3 alkyl)-(C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0120] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0121] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -(CH2) q OH, and q is an integer of 0 to 6. 4 is -(CH2) q OH and q is an integer from 0 to 2. In some embodiments, R 4 is —OH. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0122] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-C 1-6 In some embodiments, R 4 is -C(O)-C 1-3 In some embodiments, R 4 is —C(O)CH. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0123] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -P(O)(C 1-6 In some embodiments, R 4 is -P(O)(C 1-3 In some embodiments, R 4 is -P(O)(CH3)2. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0124] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 1 and X 2each independently represents N or C(R 5 In some embodiments, X 1 and X 2 Each of X is N. In some embodiments, 1 and X 2 Each of C(R 5 In some embodiments, X 1 and X 2 On the other hand, CR 5 and X 1 and X 2 and the other is N. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0125] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 1 and X 2 On the other hand, CR 5 and X 1 and X 2 The other is R 4 , and together with the atoms to which they are attached, R b In some embodiments, X is C, forming a 5- to 10-membered heterocyclyl optionally substituted with one or more of: 1 and X 2 On the other hand, CR 5 and X 1 and X 2 The other is R 4 , and together with the atoms to which they are attached, R b and C forming a 5-8 membered heterocyclyl optionally substituted with one or more of: In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0126] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b Halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl is one or more halo, OH, or -S(O)2-C 1-6 optionally substituted with alkyl, R b C 3-10 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R b Halo, oxo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 cycloalkyl, and 3- to 6-membered heterocyclyl, R b C 1-3 Alkyl is one or more halo, OH, or -S(O)2-C 1-3 optionally substituted with alkyl, R b C 3-6 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R b is oxo, -S(O)2CH3, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0127] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is, independently at each occurrence, halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl can be one or more of halo, OH, -S(O)2-C 1-6 Alkyl, or C 3-10 optionally substituted with cycloalkyl, R b C 1-6 Alkyl C 3-10 Cycloalkyl is one or more C 1-6 optionally further substituted with alkyl or —OH; R b C 3-10 Cycloalkyl is a group consisting of one or more -OH, C 3-10 Cycloalkyl, or C 1-6 optionally substituted with alkyl, R b C 3-10 Cycloalkyl C 1-6 The alkyl is optionally further substituted with one or more —OH. In some embodiments, R b is, independently at each occurrence, halo, oxo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3alkyl)2, -S(O)2-R a , C 3-6 cycloalkyl, and 3- to 6-membered heterocyclyl; R b C 1-3 Alkyl can be one or more of halo, OH, -S(O)2-C 1-3 Alkyl, or C 3-6 optionally substituted with cycloalkyl, R b C 1-3 Alkyl C 3-6 Cycloalkyl is one or more C 1-3 optionally further substituted with alkyl or —OH; R b C 3-6 Cycloalkyl is a group consisting of one or more -OH, C 3-6 Cycloalkyl, or C 1-3 optionally substituted with alkyl, R b C 3-6 Cycloalkyl C 1-3 The alkyl is optionally further substituted with one or more —OH. In some embodiments, R b is oxo, -S(O)2CH3, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0128] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is independently, at each occurrence, -OH, halo, oxo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10cycloalkyl, and 3- to 10-membered heterocyclyl; R b C 1-6 Alkyl can be one or more of halo, OH, -S(O)2-C 1-6 Alkyl, or C 3-10 optionally substituted with cycloalkyl, R b C 1-6 Alkyl C 3-10 Cycloalkyl is one or more C 1-6 optionally further substituted with alkyl or —OH; R b C 3-10 Cycloalkyl is a group consisting of one or more -OH, C 3-10 Cycloalkyl, or C 1-6 optionally substituted with alkyl, R b C 3-10 Cycloalkyl C 1-6 The alkyl is optionally further substituted with one or more -OH, deuterium, or halo. In some embodiments, R b is independently, at each occurrence, -OH, halo, oxo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 cycloalkyl, and 3- to 6-membered heterocyclyl; R b C 1-3 Alkyl can be one or more of halo, OH, -S(O)2-C 1-3 Alkyl, or C 3-6 optionally substituted with cycloalkyl, R b C 1-3 Alkyl C 3-6 Cycloalkyl is one or more C 1-3 optionally further substituted with alkyl or —OH; R b C 3-6 Cycloalkyl is a group consisting of one or more -OH, C 3-6 Cycloalkyl, or C 1-3 optionally substituted with alkyl, R b C3-6 Cycloalkyl C 1-3 The alkyl is optionally further substituted with one or more -OH, deuterium, or halo. In some embodiments, R b is -OH, oxo, -S(O)2CH3, [ka] is selected from the group consisting of:

[0129] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is oxo. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0130] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is C 1-6 In some embodiments, R b is one or more halo, OH, or -S(O)2-C 1-6 C optionally substituted with alkyl 1-6 In some embodiments, R b is one or more halo, OH, or -S(O)2-C 1-3 C optionally substituted with alkyl 1-3 In some embodiments, R b teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0131] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is C 1-6 In some embodiments, R b C 1-6 Alkyl can be one or more of halo, OH, -S(O)2-C 1-6 Alkyl, or C 3-10 optionally substituted with cycloalkyl, R b C 1-6 Alkyl C 3-10 Cycloalkyl is one or more C 1-6 Optionally further substituted with alkyl or —OH. In some embodiments, R b is one or more halo, OH, -S(O)2-C 1-3 Alkyl, or C 3-6 C optionally substituted with cycloalkyl 1-3 alkyl, and R b C 1-3 Alkyl C 3-6 Cycloalkyl is one or more C 1-3 Optionally further substituted with alkyl or —OH. In some embodiments, R b teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0132] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is C 1-6 In some embodiments, R b C 1-6 Alkyl can be one or more of halo, OH, -S(O)2-C 1-6 Alkyl, or C 3-10 optionally substituted with cycloalkyl, R b C 1-6 Alkyl C 3-10 Cycloalkyl is one or more C 1-6 Optionally further substituted with alkyl or —OH. In some embodiments, R b is one or more halo, OH, -S(O)2-C 1-3 Alkyl, or C 3-6 C optionally substituted with cycloalkyl 1-3 alkyl, and R b C 1-3 Alkyl C 3-6 Cycloalkyl is one or more C 1-3 Optionally further substituted with alkyl or —OH. In some embodiments, R b teeth, [ka] is selected from the group consisting of:

[0133] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is -C(O)-NH(C 1-6 In some embodiments, R b is -C(O)-NH(C 1-3 In some embodiments, R b teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0134] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is -C(O)-C 1-6 In some embodiments, R b is -C(O)-C 1-3 In some embodiments, R b teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0135] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is -S(O)2-R a and R a is C 1-6 In some embodiments, R b is -S(O)2-R a and R a is C 1-3 In some embodiments, R b is -S(O)2-R a and R a is methyl. In some embodiments, R bis —S(O)CH. In some variations, the embodiments provided herein also apply to compounds of formula (I′), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0136] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is C optionally substituted with one or more -OH 3-10 In some embodiments, R b is C optionally substituted with one or more -OH 3-6 In some embodiments, R b teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0137] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is one or more -OH, C 3-10 Cycloalkyl, or C 1-6 C optionally substituted with alkyl 3-10 is cycloalkyl, C 1-6 The alkyl is optionally further substituted with one or more —OH. In some embodiments, R b is one or more -OH, C 3-6 Cycloalkyl, or C 1-3 C optionally substituted with alkyl 3-6 is cycloalkyl, C 1-3The alkyl is optionally further substituted with one or more —OH. In some embodiments, R b teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0138] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is one or more -OH, C 3-10 Cycloalkyl, or C 1-6 C optionally substituted with alkyl 3-10 is cycloalkyl, C 1-6 The alkyl is optionally further substituted with one or more -OH, deuterium, or halo. In some embodiments, R b is one or more -OH, C 3-6 Cycloalkyl, or C 1-3 C optionally substituted with alkyl 3-6 is cycloalkyl, C 1-3 The alkyl is optionally further substituted with one or more -OH, deuterium, or halo. In some embodiments, R b teeth, [ka] is selected from the group consisting of:

[0139] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R b is a 3- to 10-membered heterocyclyl. In some embodiments, R b is a 3- to 6-membered heterocyclyl. In some embodiments, R b teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0140] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 1 and X 2 On the other hand, CR 5 and X 1 and X 2 The other is R 4 and C, which together with the atom to which they are attached form a 5- to 10-membered heteroaryl. 1 and X 2 On the other hand, CR 5 and X 1 and X 2 The other is R 4 and C, together with the atom to which they are attached, to form a 5-6 membered heteroaryl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0141] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 1 and X 2 On the other hand, CR 5 and X 1 and X 2 The other is R 4 , together with the atoms to which they are attached, can be one or more R cIn some embodiments, X is C, forming a 5-10 membered heteroaryl optionally substituted with 1 and X 2 On the other hand, CR 5 and X 1 and X 2 The other is R 4 , together with the atoms to which they are attached, can be one or more R c and C forming a 5-6 membered heteroaryl optionally substituted with. In some variations, the embodiments provided herein also apply to compounds of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0142] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R c Ha, Halo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; R c C 1-6 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl, R c C 3-10 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R c Ha, Halo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 cycloalkyl, and 3- to 6-membered heterocyclyl, R c C1-6 Alkyl is one or more -S(O)2-C 1-3 optionally substituted with alkyl, R c C 3-6 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R c is methyl, isopropyl, -S(O)2CH3, and [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0143] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R c is independently present in each occurrence, halo, C 1-6 Alkyl, -C(O)-C 1-6 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -S(O)2-R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; R c C 1-6 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl, R c C 3-10 Cycloalkyl is a group consisting of one or more -OH, or C 1-6 optionally substituted with alkyl, R c The 3- to 10-membered heterocyclyl of 1-6 optionally substituted with alkyl, C 1-6 The alkyl is optionally further substituted with one or more —OH. In some embodiments, R c is independently present in each occurrence, halo, C1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 cycloalkyl, and 3- to 6-membered heterocyclyl; R c C 1-3 Alkyl is one or more -S(O)2-C 1-3 optionally substituted with alkyl, R c C 3-6 Cycloalkyl is a group consisting of one or more -OH, or C 1-3 optionally substituted with alkyl, R c The 3- to 6-membered heterocyclyl of 1-3 optionally substituted with alkyl, C 1-3 The alkyl is optionally further substituted with one or more —OH. In some embodiments, R c is methyl, isopropyl, -S(O)2CH3, and [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0144] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R c is C 1-6 Alkyl, -S(O)2-R a In some embodiments, R c is C 1-3 In some embodiments, R c is methyl. In some embodiments, R cis isopropyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0145] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R c is one or more -S(O)2-R a C optionally substituted with 1-6 alkyl, and R a is C 1-6 In some embodiments, R c is one or more -S(O)2-R a C optionally substituted with 1-3 alkyl, and R a is C 1-3 In some embodiments, R c is one or more -S(O)2-R a C optionally substituted with 1-3 alkyl, and R a is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0146] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R c is C optionally substituted with one or more -OH 3-10 In some embodiments, R c is C optionally substituted with one or more -OH 3-6 In some embodiments, R c teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0147] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R c is one or more -OH, or C 1-6 C optionally substituted with alkyl 3-10 In some embodiments, R c is one or more -OH, or C 1-3 C optionally substituted with alkyl 3-6 In some embodiments, R c teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0148] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R c is one or more -OH, or C 1-6 3- to 10-membered heterocyclyl optionally substituted with alkyl, C 1-6 The alkyl is optionally further substituted with one or more —OH. In some embodiments, R c is one or more -OH, or C 1-3 3- to 6-membered heterocyclyl optionally substituted with alkyl, C 1-3The alkyl is optionally further substituted with one or more —OH. In some embodiments, R c teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0149] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is independently, at each occurrence, H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or -OH, and 1-6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 5 is independently, at each occurrence, H, halo, -CN, 3- to 6-membered heterocyclyl, C 1-3 Alkyl, or C 1-3 is alkoxy, and R 5 C 1-3 The alkyl is optionally substituted with one or more halo, or -OH, and 1-3 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 5 are H, Cl, F, -CN, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0150] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0151] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is halo. In some embodiments, R 5 is Cl, or F. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0152] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0153] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is C 1-6 In some embodiments, R 5 is C 1-3 In some embodiments, R5 is methyl. In some embodiments, R 5 is C 1-6 alkyl, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH. In some embodiments, R 5 is C 1-3 alkyl, and R 5 C 1-3 The alkyl is optionally substituted with one or more halo, or —OH. In some embodiments, R 5 is C 1-3 alkyl, and R 5 C 1-3 The alkyl is optionally substituted with one or more fluoro or —OH. In some embodiments, R 5 are independently methyl, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0154] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is a 3- to 10-membered heterocyclyl. In some embodiments, R 5 is a 3- to 6-membered heterocyclyl. In some embodiments, R 5 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0155] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is C optionally substituted with one or more halo 1-6 In some embodiments, R 5 is C optionally substituted with one or more halo 1-3 In some embodiments, R 5 is C optionally substituted with one or more fluoro 1-3 In some embodiments, R 5 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0156] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 6 and R 7 are each independently H or halo. In some embodiments, R 6 and R 7 are each independently H or fluoro. In some embodiments, R 6 and R 7 Each of is H. In some embodiments, R 6 and R 7 Each of R is fluoro. 6and R 7 One of the two is H and the other is R 6 and R 7 and the other is fluoro. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0157] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2 In some embodiments, the disubstituted phenyl is [ka] [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0158] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2In some embodiments, the disubstituted phenyl is [ka] [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0159] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2 In some embodiments, the disubstituted phenyl is [ka] [ka] is selected from the group consisting of:

[0160] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2In some embodiments, the trisubstituted phenyl is: [ka] [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0161] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2 In some embodiments, the trisubstituted phenyl is: [ka] [ka] is selected from the group consisting of:

[0162] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2In some embodiments, the tetrasubstituted phenyl is: [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0163] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2 In some embodiments, the disubstituted pyridine is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0164] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2In some embodiments, the trisubstituted pyridine is formed by having two groups attached meta and para to the bond of the pyridine to [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0165] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2 In some embodiments, the trisubstituted pyridine is formed by having two groups attached meta and para to the bond of the pyridine to [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0166] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2In some embodiments, the trisubstituted pyridine is formed by having two groups attached meta and para to the bond of the pyridine to [ka] is selected from the group consisting of:

[0167] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2 In some embodiments, the disubstituted pyrimidine is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0168] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2 In some embodiments, the disubstituted pyrimidine is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0169] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2 In some embodiments, the disubstituted pyrimidine is [ka] [ka] In some embodiments, the disubstituted pyrimidine is selected from the group consisting of: [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0170] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold together are L 2In some embodiments, the disubstituted pyrimidine is [ka] [ka] is selected from the group consisting of:

[0171] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0172] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0173] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0174] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0175] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0176] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0177] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] and forming a heterocycle selected from the group consisting of:

[0178] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0179] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] Form.

[0180] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0181] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0182] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In certain variations, L forms a heterocycle selected from the group consisting of 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In the given variation, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0183] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , and R 4 The rings that hold [ka] In certain variations, L forms a heterocycle selected from the group consisting of 1 , L 2 , and L 3 , and R 4 The rings that hold [ka] In the given variation, L 1 , L 2 , and L 3 , and R 4 The rings that hold [ka] Form.

[0184] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and L 3 , R 4 , R 6 , and R 7 The rings that hold [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0185] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and R 6 , and R 7 The rings that hold [ka] Form.

[0186] In some embodiments of the compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 , L 2 , and R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and R 6 , and R 7 The rings that hold [ka] In some embodiments, L 1 , L 2 , and R 6 , and R 7 The rings that hold [ka] Form.

[0187] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1 or 2 and L 2 In some embodiments, n is 2 and L 2 In some embodiments, n is 1 and L 2is O. In some embodiments, n is 1 or 2 and L 2 is -O- and R 4 is -S(O)2-R a In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0188] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, p is 0, and L 2 is O and X 1 and X 2 Each of C(R 5 ) and each R 5 are independently H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH, and R 5 C 1-6 The alkoxy is optionally substituted with one or more halo. In some embodiments, n is 1, p is 0, and L 2 is O and X 1 and X 2 Each of C(R 5 ) and each R 5 are independently H. In some embodiments, n is 1, p is 0, and L 2 is O and X 1 and X 2 Each of C(R 5 ) and R 5 One of the two is H and the other is R 5 The other is halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6The alkyl is optionally substituted with one or more halo, or -OH, and 1-6 The alkoxy is optionally substituted with one or more halo. In some embodiments, n is 1, p is 0, and L 2 is O and X 1 and X 2 Each of C(R 5 ) and each R 5 are independently halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or -OH, and 1-6 The alkoxy is optionally substituted with one or more halo. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0189] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, p is 0, and L 2 is O and X 1 and X 2 One of them is N and the other is X 1 and X 2 The other is C(R 5 ) and R 5 H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH, and R 5 C 1-6 The alkoxy is optionally substituted with one or more halo. In some embodiments, n is 1, p is 0, and L 2 is O and X 1 and X2 One of them is N and the other is X 1 and X 2 The other is C(R 5 ) and R 5 is H. In some embodiments, n is 1, p is 0, and L 2 is O and X 1 and X 2 One of them is N and the other is X 1 and X 2 The other is C(R 5 ) and R 5 -halo, -CN, 3-10 membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH, and R 5 C 1-6 The alkoxy is optionally substituted with one or more halo. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0190] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1 and L 2 is O and X 1 and X 2 is N. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0191] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, p is 0, and L 2is O and X 1 and X 2 One of them is C(R 5 ) and R 5 is H and X 1 and X 2 The other is R 4 and together with the atom to which they are attached, (i) a 5- to 10-membered heterocyclyl, which is R b or (ii) a 5- to 10-membered heteroaryl, optionally substituted with one or more R c C forming a 5-10 membered heteroaryl optionally substituted with R 6 and R 7 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0192] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1 and L 2 is O and X 1 and X 2 One of them is C(R 5 ) and R 5 H, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH, and R 5 C 1-6 The alkoxy is optionally substituted with one or more halo, and X 1 and X 2 The other is R 4 and together with the atom to which they are attached, (i) a 5- to 10-membered heterocyclyl, which is R bor (ii) a 5- to 10-membered heteroaryl, optionally substituted with one or more R c C forming a 5-10 membered heteroaryl optionally substituted with R 6 and R 7 Each of is H. In some embodiments, n is 1 and L 2 is O and X 1 and X 2 One of them is C(R 5 ) and R 5 is H and X 1 and X 2 The other is R 4 and together with the atom to which they are attached, (i) a 5- to 10-membered heterocyclyl, which is R b or (ii) a 5- to 10-membered heteroaryl, optionally substituted with one or more R c C forming a 5-10 membered heteroaryl optionally substituted with R 6 and R 7 Each of is H. In some embodiments, n is 1 and L 2 is O and X 1 and X 2 One of them is C(R 5 ) and R 5 -halo, -CN, 3-10 membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH, and R 5 C 1-6 The alkoxy is optionally substituted with one or more halo, and X 1 and X 2 The other is R 4 and together with the atom to which they are attached, (i) a 5- to 10-membered heterocyclyl, which is R bor (ii) a 5- to 10-membered heteroaryl, optionally substituted with one or more R c C forming a 5-10 membered heteroaryl optionally substituted with R 6 and R 7 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0193] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, n is 1, p is 0, and L 2 is O and X 1 and X 2 One of them is N and the other is X 1 and X 2 The other is R 4 and together with the atom to which they are attached, (i) a 5- to 10-membered heterocyclyl, which is R b or (ii) a 5- to 10-membered heterocyclyl optionally substituted with one or more of R c 5-10 membered heteroaryl optionally substituted with R 6 and R 7 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0194] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 2; n is an integer from 1 to 2; p is an integer from 0 to 2; R 1 If present, each occurrence independently represents halo, -CN, C 1-3 Alkoxy, or C 1-3 is selected from the group consisting of alkyl, R 1 C 1-3 the alkoxy is optionally substituted with one or more halo; R 1 C 1-3 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-3 Alkyl, C 3-6 cycloalkyl, or 3- to 10-membered heterocyclyl; R 2 C 1-3 Alkyl is one or more of halo, -OH, -NH2, or C 1-3 optionally substituted with alkoxy; R 2 C 3-6 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-3 is alkyl; L 1 is C 1-3 alkylene, and L 1 C 1-3 Alkylene is one or more C 1-3 optionally substituted with alkyl, C 1-3 Alkyl is one or more -OH or C 1-3 optionally further substituted with alkoxy; L 2 is O or N(R x ) and R x is H or C 1-3 is alkyl; (1)L 3 is absent or O, C 3-6 Cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 is alkylene, C 3-6 Cycloalkyl is a group consisting of one or more -OH, or C 1-3 optionally substituted with alkyl; L 3 C 1-3 Alkylene is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; The 3- to 10-membered heterocyclyl is optionally substituted with one or more -OH; X 1 and X 2 are each independently N or -C(R 5 ) and; R4 is (i)-S(O)2-R a ; (ii) 5- to 10-membered heteroaryl, R 4 The 5- to 10-membered heteroaryl may be one or more C 1-3 optionally substituted with alkyl; (iii)-N(R d )2, and R d is independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-3 alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-3 alkyl)2, and C 1-3 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-3 alkyl, a 3- to 10-membered heterocycle, the 3- to 10-membered heterocycle being optionally substituted with one or more oxo, or both R e together with the N to which they are attached to form a 3- to 10-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-3 Alkyl, -OH, oxo or -S(O)R a 3- to 10-membered heterocyclyl optionally substituted with (vii)-S(O)-N(C 1-3 alkyl)-(C 1-3 alkyl), (viii)-CN, (ix)-(CH2) q OH, where q is an integer from 0 to 4; (x)-C(O)-C 1-3 alkyl, or (xi)-P(O)(C 1-3 alkyl)2; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 10-membered heterocyclyl or a 5- to 10-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b optionally substituted with R b is, independently at each occurrence, halo, oxo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 selected from the group consisting of cycloalkyl, and 3- to 6-membered heterocyclyl; R b C 1-3 Alkyl can be one or more of halo, OH, -S(O)2-C 1-3 Alkyl, or C 3-6 optionally substituted with cycloalkyl; R b C 1-3Alkyl C 3-6 Cycloalkyl is one or more C 1-3 optionally further substituted with alkyl or —OH; R b C 3-6 Cycloalkyl is a group consisting of one or more -OH, C 3-6 Cycloalkyl, or C 1-3 optionally substituted with alkyl; R b C 3-6 Cycloalkyl C 1-3 The alkyl is optionally further substituted with one or more -OH; A 5- to 10-membered heteroaryl may have one or more R c optionally substituted with R c is independently present in each occurrence, halo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 selected from the group consisting of cycloalkyl, and 3- to 6-membered heterocyclyl; R c C 1-3 Alkyl is one or more -S(O)2-C 1-6 optionally substituted with alkyl; R c C 3-6 Cycloalkyl is a group consisting of one or more -OH or C 1-6 optionally substituted with alkyl; R c 3-6 membered heterocyclyl is one or more -OH or C 1-3 optionally substituted with alkyl; R c 3-6 membered heterocyclyl C 1-3 The alkyl is optionally further substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-3Alkyl, or -N(C 1-3 alkyl)-C(O)-C 1-3 C optionally substituted with alkyl 1-3 Alkyl, (ii) one or more -OH, -C(O)2-C 1-3 Alkyl, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, or -C(O)-C 3-6 Heterocyclyl, or C 1-3 C optionally substituted with alkyl 3-6 Cycloalkyl, C 1-3 Alkyl is optionally substituted with one or more -OH, or (iii) one or more C 1-3 a 3- to 6-membered heterocyclyl optionally substituted with alkyl; R 5 is independently, at each occurrence, H, halo, -CN, 3- to 6-membered heterocyclyl, C 1-3 Alkyl, or C 1-3 is alkoxy, and R 5 C 1-3 The alkyl is optionally substituted with one or more halo or —OH, and R 5 C 1-3 The alkoxy is optionally substituted with one or more halo; R 6 and R 7 are each independently H or halo. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0195] In some embodiments of the compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 2; n is an integer from 1 to 2; p is an integer from 0 to 1; R 1If present, each occurrence independently represents Cl, Br, F, I, -CN, C 1-3 Alkoxy, or C 1-3 is selected from the group consisting of alkyl, R 1 C 1-3 The alkoxy is optionally substituted with one or more F; R 1 C 1-3 alkyl is optionally substituted with one or more F; R 2 is H, C 1-3 Alkyl, C 3-4 cycloalkyl, or 3- to 4-membered heterocyclyl; R 2 C 1-3 The alkyl is optionally substituted with one or more F, —OH, —NH2, or —OCH3; R 2 C 3-4 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-3 is alkyl; L 1 is C 1-3 alkylene, and L 1 C 13 alkylene optionally substituted with one or more methyl, which methyl is optionally further substituted with one or more -OH or -OCH; L 2 is O; (1)L 3 is absent or O, C 3-4 Cycloalkyl, 3- to 7-membered heterocyclyl, or C 1-4 is alkylene, C 3-4 cycloalkyl is optionally substituted with one or more -OH, or -CH; L 3 C 1-6 The alkylene is optionally substituted with one or more -OH, -CH3; X 1 and X 2 are each independently N or C(R5 ) and; R4 is (i)-S(O)2-R a ; (ii) 5- to 6-membered heteroaryl, R 4 wherein the 5-6 membered heteroaryl is optionally substituted with one or more -CH3; (iii)-N(R d )2, and R d are independently H, C 1-3 Alkyl, or -S(O)2-R a and R d C 1-3 alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(CH3)2 (v)-C(O)-N(R e )2, and R e is independently at each occurrence H, CH, or a 3- to 6-membered heterocycle, wherein the 3- to 6-membered heterocycle is optionally substituted with one or more oxo, or both R e together with the N to which they are attached to form a 3- to 7-membered heterocyclyl, which may be one or more of F, oxo, -OH, NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-3 Alkyl, -OH, oxo or -S(O)R a 3- to 7-membered heterocyclyl optionally substituted with (vii) -S(O)-N(CH3)-(CH3), (viii)-CN, (ix)-(CH2) q OH, where q is an integer from 0 to 2; or (x)-C(O)-CH3, or (xi) -P(O)(CH3)2; or (2)L 3 is non-existence; X 1 and X 2One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 8-membered heterocyclyl or a 5- to 6-membered heteroaryl; A 5- to 8-membered heterocyclyl may have one or more R b optionally substituted with R b is independently at each occurrence oxo, C 1-3 Alkyl, -C(O)-CH3, -C(O)-NH2, -C(O)-NH(CH3), -C(O)-N(CH3)2, -S(O)2-R a , C 3-4 selected from the group consisting of cycloalkyl, and 3- to 4-membered heterocyclyl; R b C 1-3 Alkyl is one or more of F, OH, -S(O)2-CH3, or C 3-4 optionally substituted with cycloalkyl; R b C 1-3 Alkyl C 3-4 The cycloalkyl is optionally further substituted with one or more CH3 or -OH; R b C 3-4 Cycloalkyl is a group consisting of one or more -OH, C 3-4 Cycloalkyl, or C 1-3 optionally substituted with alkyl; R b C 3-4 Cycloalkyl C 1-3 The alkyl is optionally further substituted with one or more -OH; 5-6 membered heteroaryl is one or more R c optionally substituted with R c is independently in each occurrence, C 1-3 Alkyl, -S(O)2-R a , C 3-4 selected from the group consisting of cycloalkyl, and 3- to 4-membered heterocyclyl; R c C 1-6The alkyl is optionally substituted with one or more -S(O)2-CH3; R c C 3-4 Cycloalkyl is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; R c wherein the 3- to 4-membered heterocyclyl is optionally substituted with one or more —OH or methyl; R c wherein the methyl of the 3-4 membered heterocyclyl is optionally further substituted with one or more -OH; Either R a is independent in each occurrence, (i) C optionally substituted with one or more F, -OH, -S(O)2-CH3, or -N(CH3)-C(O)-CH3 1-3 Alkyl, (ii) one or more of -OH, -C(O)2-CH3, -C(O)-NH(CH3), -C(O)-N(CH3)2, or -C(O)-C 3-4 C optionally substituted with heterocyclyl or methyl 3-4 cycloalkyl, wherein methyl is optionally substituted with one or more -OH; or (iii) a 3- to 4-membered heterocyclyl optionally substituted with one or more methyl; R 5 is independently, at each occurrence, H, Cl, F, —CN, 3- to 4-membered heterocyclyl, C 1-3 Alkyl, or C 1-3 is alkoxy, and R 5 C 1-3 Alkyl is optionally substituted with one or more F or —OH, and R 5 C 1-3 The alkoxy is optionally substituted with one or more F; R 6 and R 7are each independently H or F. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0196] In some embodiments of a compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 2; n is an integer from 1 to 2; p is an integer from 0 to 1; R 1 If present, each occurrence independently represents halo, -CN, C 1-3 Alkoxy, and C 1-3 is selected from the group consisting of alkyl, R 1 C 1-3 the alkoxy is optionally substituted with one or more halo; R 1 C 1-3 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-3 Alkyl, C 3-6 cycloalkyl, or 3- to 6-membered heterocyclyl; R 2 C 1-6 Alkyl is a group consisting of one or more deuterium, halo, -OH, -NH2, or C 1-3 optionally substituted with alkoxy; R 2 C 3-6 cycloalkyl is optionally substituted with one or more -OH; R 3 If present, C 1-3 is alkyl; L 1 is C 1-3 is alkylene, L 1 C 1-6 Alkylene is a group consisting of one or more deuterium or C1-3 optionally substituted with alkyl; C 1-3 Alkyl is one or more -OH or C 1-3 optionally further substituted with alkoxy; L 2 is O; (1)L 3 is absent or O, C 3-6 Cycloalkyl, 3- to 6-membered heterocyclyl, or C 1-3 is alkylene, L 3 C 3-6 Cycloalkyl is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; L 3 C 1-3 Alkylene is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; C 1-3 The alkyl is optionally substituted with one or more -OH; L 3 3-6 membered heterocyclyl is one or more -OH or C 1-3 optionally substituted with alkyl; X 1 and X 2 are each independently N or C(R 5 ) and; R 4 teeth, (i)-S(O)2-R a ; (ii) 5- to 10-membered heteroaryl, R 4 The 5- to 10-membered heteroaryl may be one or more C 1-3 optionally substituted with alkyl; (iii)-N(R d )2, and R d is independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-3 alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-3 alkyl)2, and C 1-3 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-3 alkyl, or a 3- to 6-membered heterocycle; R e is optionally substituted with one or more oxo, or both R e together with the N to which they are attached form a 3- to 6-membered heterocyclyl; 3- to 6-membered heterocyclyl may be one or more of halo, oxo, -OH, NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-3 Alkyl, -OH, oxo or -S(O)R a 3- to 6-membered heterocyclyl optionally substituted with (vii)-S(O)-N(C 1-3 alkyl)-(C 1-3 alkyl), (viii)-CN, (ix)-(CH2) q OH, where q is an integer from 0 to 3; (x)-C(O)-C 1-3 alkyl, or (xi)-P(O)(C 1-3 alkyl)2; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 8-membered heterocyclyl or a 5- to 10-membered heteroaryl; A 5- to 8-membered heterocyclyl may have one or more R b is optionally replaced by R b is independently, at each occurrence, -OH, halo, oxo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 selected from the group consisting of cycloalkyl, and 3- to 6-membered heterocyclyl; R b C 1-3 Alkyl can be one or more of halo, OH, -S(O)2-C 1-3 Alkyl, or C 3-6 optionally substituted with cycloalkyl; R b C 1-3 Alkyl C 3-6 Cycloalkyl is one or more C 1-3 optionally further substituted with alkyl or —OH; R b C 3-6 Cycloalkyl is a group consisting of one or more -OH, C 3-6 Cycloalkyl, or C 1-3 optionally substituted with alkyl; R b C 3-6 Cycloalkyl C 1-3 the alkyl is optionally further substituted with one or more -OH, deuterium, or halo; A 5- to 10-membered heteroaryl may have one or more R c is optionally replaced by R c is independently present in each occurrence, halo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6selected from the group consisting of cycloalkyl, and 3- to 6-membered heterocyclyl; R c C 1-3 Alkyl is one or more -S(O)2-C 1-3 optionally substituted with alkyl; R c C 3-6 Cycloalkyl is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; R c 3-6 membered heterocyclyl is one or more -OH or C 1-3 optionally substituted with alkyl; R c 3-6 membered heterocyclyl C 1-3 The alkyl is optionally further substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-3 Alkyl, or -N(C 1-3 alkyl)-C(O)-C 1-3 C optionally substituted with alkyl 1-3 Alkyl, (ii) one or more -OH, -C(O)2-C 1-3 Alkyl, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, or -C(O)-C 3-6 Heterocyclyl, or C 1-3 C optionally substituted with alkyl 3-6 cycloalkyl, C 1-3 alkyl optionally substituted with one or more -OH; (iii) one or more C 1-3 a 3- to 6-membered heterocyclyl optionally substituted with alkyl, or (iv) NH(C 1-3 alkyl); R 5 is independently, at each occurrence, H, halo, -CN, 3- to 6-membered heterocyclyl, C1-3 Alkyl, or C 1-3 is an alkoxy; R 5 C 1-3 the alkyl is optionally substituted with one or more halo or -OH; R 1 C 1-3 The alkoxy is optionally substituted with one or more halo; X 3 is N or C(R 6 ) and; X 4 is N or C(R 7 ) and; R 6 and R 7 are each independently H or halo.

[0197] In some embodiments of a compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 2; n is 1; p is an integer equal to 0; R 1 If present, each occurrence independently represents halo, -CN, C 1-3 Alkoxy, and C 1-3 is selected from the group consisting of alkyl, R 1 C 1-3 the alkoxy is optionally substituted with one or more halo; R 1 C 1-3 The alkyl is optionally substituted with one or more halo; R 2 is H, C 1-3 Alkyl, C 3-6 cycloalkyl, or 3- to 6-membered heterocyclyl; R 2 C 1-6 Alkyl is a group consisting of one or more deuterium, halo, -OH, -NH2, or C 1-3 optionally substituted with alkoxy; R 2 C 3-6cycloalkyl is optionally substituted with one or more -OH; L 1 is C 1-3 is alkylene, L 1 C 1-6 The alkylene is optionally substituted with one or more deuterium atoms; L 2 is O; (1)L 3 is absent or O, C 3-6 Cycloalkyl, 3- to 6-membered heterocyclyl, or C 1-3 is alkylene, L 3 C 3-6 Cycloalkyl is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; L 3 C 1-3 Alkylene is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; C 1-3 The alkyl is optionally substituted with one or more -OH; L 3 3-6 membered heterocyclyl is one or more -OH or C 1-3 optionally substituted with alkyl; X 1 and X 2 are each independently N or C(R 5 ) and; R 4 teeth, (i)-S(O)2-R a ; (ii) 5- to 10-membered heteroaryl, R 4 The 5- to 10-membered heteroaryl may be one or more C 1-3 optionally substituted with alkyl; (iii)-N(R d )2, and R d is independently at each occurrence H, C alkyl, or -S(O)-R a and R d C 1-3alkyl optionally substituted with one or more -OH; (iv) -NS(O)-(C 1-3 alkyl)2, and C 1-3 alkyl optionally substituted with one or more -OH; (v)-C(O)-N(R e )2, and R e are independently H, C 1-3 alkyl, or a 3- to 6-membered heterocycle; R e is optionally substituted with one or more oxo, or both R e together with the N to which they are attached form a 3- to 6-membered heterocyclyl; 3- to 6-membered heterocyclyl may be one or more of halo, oxo, -OH, NH, -NH-S(O)-R a , or -S(O)2-R a optionally substituted with (vi) one or more C 1-3 Alkyl, -OH, oxo or -S(O)R a 3- to 6-membered heterocyclyl optionally substituted with (ix)-(CH2) q OH, where q is an integer from 0 to 3; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 8-membered heterocyclyl or a 5- to 10-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b is optionally replaced by R b is independently, at each occurrence, -OH, halo, oxo, C 1-3 Alkyl, -C(O)-C 1-3Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 selected from the group consisting of cycloalkyl, and 3- to 6-membered heterocyclyl; R b C 1-3 Alkyl can be one or more of halo, OH, -S(O)2-C 1-3 Alkyl, or C 3-6 optionally substituted with cycloalkyl; R b C 1-3 Alkyl C 3-6 Cycloalkyl is one or more C 1-3 optionally further substituted with alkyl or —OH; R b C 3-6 Cycloalkyl is a group consisting of one or more -OH, C 3-6 Cycloalkyl, or C 1-3 optionally substituted with alkyl; R b C 3-6 Cycloalkyl C 1-3 the alkyl is optionally further substituted with one or more -OH, deuterium, or halo; A 5- to 10-membered heteroaryl may have one or more R c is optionally replaced by R c is independently present in each occurrence, halo, C 1-3 Alkyl, -C(O)-C 1-3 Alkyl, -C(O)-NH2, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -S(O)2-R a , C 3-6 selected from the group consisting of cycloalkyl, and 3- to 6-membered heterocyclyl; R c C 1-3 Alkyl is one or more -S(O)2-C 1-3 optionally substituted with alkyl; R c C3-6 Cycloalkyl is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; R c 3-6 membered heterocyclyl is one or more -OH or C 1-3 optionally substituted with alkyl; R c 3-6 membered heterocyclyl C 1-3 The alkyl is optionally further substituted with one or more -OH; Either R a is independent in each occurrence, (i) one or more halo, -OH, -S(O)2-C 1-3 Alkyl, or -N(C 1-3 alkyl)-C(O)-C 1-3 C optionally substituted with alkyl 1-3 Alkyl, (ii) one or more -OH, -C(O)2-C 1-3 Alkyl, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, or -C(O)-C 3-6 Heterocyclyl, or C 1-3 C optionally substituted with alkyl 3-6 cycloalkyl, C 1-3 alkyl optionally substituted with one or more -OH; (iii) one or more C 1-3 a 3- to 6-membered heterocyclyl optionally substituted with alkyl, or (iv) NH(C 1-3 alkyl); R 5 is independently, at each occurrence, H, halo, -CN, 3- to 6-membered heterocyclyl, C 1-3 Alkyl, or C 1-3 is an alkoxy; R 5 C 1-3 the alkyl is optionally substituted with one or more halo or -OH; R 1 C 1-3The alkoxy is optionally substituted with one or more halo; X 3 is N or C(R 6 ) and; X 4 is N or C(R 7 ) and; R 6 and R 7 are each independently H or halo.

[0198] In some embodiments of a compound of Formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 2; n is 1; p is an integer equal to 0; R 1 If present, each occurrence independently represents halo, -CN, C 1-3 Alkoxy, and C 1-3 is selected from the group consisting of alkyl, R 1 C 1-3 the alkoxy is optionally substituted with one or more halo; R 1 C 1-3 The alkyl is optionally substituted with one or more halo; R 2 is H; L 1 is C 1-3 is alkylene, L 1 C 1-6 The alkylene is optionally substituted with one or more deuterium atoms; L 2 is O; (1)L 3 is non-existent, or C 1-3 is alkylene, L 3 C 1-3 Alkylene is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; X 1 and X 2are each independently N or C(R 5 ) and; R 4 teeth, (i)-S(O)2-R a ; (ii)-(CH2) q OH, where q is an integer from 0 to 3; or (2)L 3 is non-existence; X 1 and X 2 One of the two is N or C(R 5 ) and; X 1 and X 2 The other is R 4 and N or C, which together with the atom to which they are attached form a 5- to 8-membered heterocyclyl or a 5- to 20-membered heteroaryl; A 5- to 10-membered heterocyclyl may have one or more R b is optionally replaced by R b is independently oxo, or C 3-6 is cycloalkyl, C 3-6 Cycloalkyl is a group consisting of one or more -OH, C 3-6 Cycloalkyl, or C 1-3 optionally substituted with alkyl; A 5- to 10-membered heteroaryl may have one or more R c is optionally replaced by R c is independently in each occurrence, C 1-3 Alkyl, C 3-6 cycloalkyl; R c C 3-6 Cycloalkyl is a group consisting of one or more -OH or C 1-3 optionally substituted with alkyl; Either R a is independent in each occurrence, (I C 1-3 Optionally substituted with alkyl and one or more halo, -OH, -S(O)2-C 1-3Alkyl, or -N(C 1-3 alkyl)-C(O)-C 1-3 is alkyl; R 5 are independently in each occurrence H, halo, C 1-3 Alkyl, or C 1-3 is an alkoxy; R 5 C 1-3 the alkyl is optionally substituted with one or more halo or -OH; R 1 C 1-3 The alkoxy is optionally substituted with one or more halo; X 3 is N or C(R 6 ) and; X 4 is N or C(R 7 ) and; R 6 and R 7 are each independently H or halo.

[0199] In some embodiments, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (IA): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein n is 1 or 2; m, p, R 1 , R 2 , R 3 , L 1 , L 3 , R 4 , X 1 , X 2 , R 6 , and R 7 are as defined for formula (I). In some variations, m, p, R of formula (IA) 1 , R 2 , R 3 , L 1 , L 3 , R4 , X 1 , X 2 , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0200] In some embodiments, provided herein is a compound of Formula (I) or Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of Formula (I-A1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , L 3 , R 4 , X 1 , X 2 , R 6 , and R 7 are as defined for formula (I). In some variations, m, p, R of formula (I-A1) 1 , R 2 , R 3 , L 1 , L 3 , R 4 , X 1 , X 2 , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0201] In some embodiments of a compound of Formula (I), (IA) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0202] In some embodiments of a compound of Formula (I), (IA), or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0203] In some embodiments of a compound of Formula (I), (IA), or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, p is an integer from 0 to 10. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0204] In some embodiments of a compound of Formula (I), (IA) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is C 1-6 In some embodiments, L is alkylene.1 is C 1-3 In some embodiments, L is alkylene. 1 is ethylene. In some embodiments, L 1 teeth, [ka] where # indicates the point of attachment to -O- and ## indicates the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0205] In some embodiments of a compound of Formula (I), (IA) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0206] In some embodiments of a compound of Formula (I), (IA) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-3 In some embodiments, R 4 is -S(O)2-R a and R a is methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0207] In some embodiments of compounds of Formula (I), (IA) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 1 and X 2 Each of C(R 5 In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0208] In some embodiments of a compound of Formula (I), (IA) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0209] In some embodiments of a compound of Formula (I), (IA) or (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 6 and R 7is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0210] In some embodiments, provided herein is a compound of Formula (I) or Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of Formula (I-A2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , L 3 , R 4 , X 1 , X 2 , R 6 , and R 7 are as defined for formula (I). In some variations, m, p, R of formula (I-A2) 1 , R 2 , R 3 , L 1 , L 3 , R 4 , X 1 , X 2 , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0211] In some embodiments, provided herein is a compound of Formula (I) or Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of Formula (I-A3): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein n is 1 or 2; m, n, p, R 1 , R 2 , R 3 , L 1 , X 1 , X 2 , R 6 , R 7 , and R a are as defined for formula (I). In some variations, m, n, p, R of formula (I-A3) 1 , R 2 , R 3 , L 1 , X 1 , X 2 , R 6 , R 7 , and R a is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0212] In some embodiments, provided herein is a compound of Formula (I), (IA), or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (IB): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , L 3 , R 4 , R 5 , R 6 , and R 7are as defined for formula (I). In some variations, m, p, R of formula (IB) 1 , R 2 , R 3 , L 1 , L 3 , R 4 , R 5 , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0213] In some embodiments, provided herein is a compound of Formula (I), (IA), (I-A2), or (IB) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-B1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, R 1 , R 2 , L 1 , L 3 , R 4 , R 6 , and R 7 is as defined for formula (I). In some variations, m, R in formula (I-B1) 1 , R 2 , L 1 , L 3 , R 4 , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0214] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0215] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 In some embodiments, R 2 is C 1-3 In some embodiments, R 2 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0216] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is one or more halo, -OH, or C 1-6 C optionally substituted with alkoxy 1-6 In some embodiments, R 2 is one or more halo, -OH, or C 1-3 C optionally substituted with alkoxy 1-3 In some embodiments, R 2 is one or more halo, -OH, NH2, or C 1-3In some embodiments, R is ethyl optionally substituted with alkoxy. 2 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0217] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is one or more deuterium, halo, -OH, or C 1-6 C optionally substituted with alkoxy 1-6 In some embodiments, R 2 is one or more deuterium, halo, -OH, or C 1-3 C optionally substituted with alkoxy 1-3 In some embodiments, R 2 is one or more deuterium halo, -OH, NH2, or C 1-3 In some embodiments, R is methyl optionally substituted with alkoxy. 2 is one or more deuterium halo, -OH, NH2, or C 1-3 In some embodiments, R is ethyl optionally substituted with alkoxy. 2 teeth, [ka] is selected from the group consisting of:

[0218] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C optionally substituted with one or more -OH 3-10 In some embodiments, R 2 is C optionally substituted with one or more -OH 3-6 In some embodiments, R 2 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0219] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is a 3- to 15-membered heterocyclyl. In some embodiments, R 2 is a 3- to 6-membered heterocyclyl. In some embodiments, R 2 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0220] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0221] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some embodiments, R 1 is Br. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0222] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is C 1-6 In some embodiments, R 1 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0223] In some embodiments of a compound of Formula (I'), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is C 1-6 alkyl, and R 1 C 1-6 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is C 1-3 alkyl, and R 1 C 1-3 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is methyl and R 1 The methyl in R is optionally substituted with one or more F. In some embodiments, R 1 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0224] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0225] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, p is an integer from 0 to 10. In some embodiments, p is 0. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0226] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is C 1-6 alkylene, and L 1 C 1-6 Alkylene is one or more C 1-6 In some embodiments, L is optionally substituted with alkyl. 1 is one or more C 1-3 C optionally substituted with alkyl 1-3 In some embodiments, L is alkylene. 1 is one or more C 1-6 In some embodiments, L is ethylene optionally substituted with alkyl. 1 teeth, [ka] and each L is selected from the group consisting of 1 where # indicates the point of attachment to -O- and ## indicates the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0227] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0228] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 In some embodiments, L is alkylene. 3 is C 1-3 In some embodiments, L is alkylene. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0229] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 3-10 is cycloalkyl, and L 3 C 3-10 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 is C 3-8 is cycloalkyl, and L 3 C3-8 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I') or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0230] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is 3-10 membered heterocyclyl. In some embodiments, L 3 is a 3- to 6-membered heterocyclyl. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0231] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is 3-10 membered heterocyclyl. In some embodiments, L 3 is a 3- to 6-membered heterocyclyl. 3 teeth, [ka] is selected from the group consisting of:

[0232] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-6 alkyl, and R a C 1-6 Alkyl can be one or more of halo, -OH, -S(O)2-C 1-6 Alkyl, or -N(C 1-6 alkyl)-C(O)-C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-3 alkyl, and R a C 1-3 Alkyl can be one or more of halo, -OH, -S(O)2-C 1-3 Alkyl, or -N(C 1-3 alkyl)-C(O)-C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0233] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 teeth, [ka] is selected from the group consisting of:

[0234] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 3-10 is cycloalkyl. R 4 is -S(O)2-R a and R a is C 3-10 is cycloalkyl, and R a C 3-10 Cycloalkyl is a group consisting of one or more -OH, C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -C(O)-C 3-10 Heterocyclyl or C 1-6 optionally substituted with alkyl, C 1-6 The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 is -S(O)2-R a and R a is C 3-6 is cycloalkyl, and R a C 3-6 Cycloalkyl is a group consisting of one or more -OH, C(O)2-C 1-6 Alkyl, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -C(O)-C 3-10 Heterocyclyl, or C 1-6optionally substituted with alkyl, C 1-6 The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 is -S(O)2-R a and R a is C 3-6 is cycloalkyl, and R a C 3-6 Cycloalkyl is a group consisting of one or more -OH, C(O)2-C 1-3 Alkyl, -C(O)-NH(C 1-3 alkyl), -C(O)-N(C 1-3 alkyl)2, -C(O)-C 3-6 Heterocyclyl, or C 1-3 optionally substituted with alkyl, C 1-3 The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0235] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is a 3- to 10-membered heterocyclyl. In some embodiments, R 4 is -S(O)2-R a and R a is a 3- to 10-membered heterocyclyl, and R a The 3- to 10-membered heterocyclyl may have one or more C 1-6 In some embodiments, R 4is -S(O)2-R a and R a is a 3- to 6-membered heterocyclyl, and R a The 3- to 6-membered heterocyclyl may have one or more C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is a 3- to 6-membered heterocyclyl, and R a The 3- to 6-membered heterocyclyl may have one or more C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0236] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is a 5- to 20-membered heteroaryl. In some embodiments, R 4 is one or more C 1-6 In some embodiments, R is a 5- to 20-membered heteroaryl optionally substituted with alkyl. 4 is one or more C 1-6 In some embodiments, R is a 5- to 6-membered heteroaryl optionally substituted with alkyl. 4 is one or more C 1-3 In some embodiments, R is a 5- to 6-membered heteroaryl optionally substituted with alkyl. 4 is a 5-6 membered heteroaryl optionally substituted with one or more methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0237] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -N(R d )2 and R d are each independently H or C alkyl, and R d C 1-6 Alkyl is one or more -OH or -S(O)2-R a optionally substituted with R a is C 1-6 In some embodiments, R 4 is -N(R d )2 and R d are each independently H or C alkyl, and R d C 1-3 Alkyl is one or more -OH or -S(O)2-R a optionally substituted with R a is C 1-3 In some embodiments, R 4 is -N(R d )2 and R d each independently represents H, or C 1-3 alkyl, and R d C 1-3 Alkyl is one or more -OH or -S(O)2-R a optionally substituted with R a is methyl. In some embodiments, R 4 is -NH2, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0238] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2 and R e each independently represents H or C 1-6 In some embodiments, R 4 is -C(O)-N(R e )2 and R e each independently represents H or C 1-3 In some embodiments, R 4 is -C(O)-N(R e )2 and R e Each of R is independently H or methyl. 4 is —C(O)—NH. In some embodiments, R 4 is —C(O)—NH(CH). In some embodiments, R 4 is —C(O)—N(CH) 2. In some variations, the embodiments provided herein also apply to compounds of formula (I′), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0239] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(Re )2, and both R e together with the N to which they are attached form a 3- to 10-membered heterocyclyl. In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached to form a 3- to 10-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, NH-S(O)-R a , or -S(O)2-R a optionally substituted with R a is C 1-6 In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached to form a 3- to 7-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, NH-S(O)-R a , or -S(O)2-R a optionally substituted with R a is C 1-3 In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached to form a 3- to 7-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, NH-S(O)-R a , or -S(O)2-R a optionally substituted with R a is methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0240] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is a 3- to 10-membered heterocyclyl optionally substituted with one or more oxo. In some embodiments, R 4 is a 3- to 7-membered heterocyclyl optionally substituted with one or more oxo. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0241] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -NS(O)-(C 1-6 In some embodiments, R 4 is -NS(O)-(C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0242] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)-N(C 1-6 alkyl)-(C 1-6 In some embodiments, R 4 is -S(O)-N(C 1-3 alkyl)-(C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0243] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0244] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -P(O)(C 1-6 In some embodiments, R 4 is -P(O)(C 1-3 In some embodiments, R 4 is -P(O)(CH3)2. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0245] In some embodiments, provided herein is a compound of Formula (I), (IA), (I-A2), or (IB) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-B2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, 5 -halo, -CN, 3-10 membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or -OH, and 1-6 Alkoxy is optionally substituted with one or more halo; m, R 1 , R 2 , L 1 , L 3 , R 4 , R 6 , and R 7 is as defined for formula (I). In some variations, m, R in formula (I-B2) 1 , R 2 , L 1 , L 3 , R4 , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0246] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0247] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, and R 2 C 1-6 The alkyl is optionally substituted with one or more halo, -OH. In some embodiments, R 2 is C 1-3 alkyl, and R 2 C 1-3 The alkyl is optionally substituted with one or more halo, -OH. In some embodiments, R 2 is methyl. In some embodiments, R 2 is ethyl, and R 2 The ethyl in R is optionally substituted with one or more halo, —OH. 2 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0248] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, and R 2 C 1-6 Alkyl is optionally substituted with one or more deuterium atoms. In some embodiments, R 2 is C 1-3 alkyl, and R 2 C 1-3 Alkyl is optionally substituted with one or more deuterium atoms. In some embodiments, R 2 is methyl and R 2 The methyl in R is optionally substituted with one or more deuterium atoms. 2 teeth, [ka] is.

[0249] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is 1. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0250] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0251] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0252] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is one or more C 1-6 C optionally substituted with alkyl 1-6 alkylene, C 1-6 Alkyl is -OH or C 1-6 In some embodiments, L is optionally substituted with alkoxy. 1 is methylene. In some embodiments, L 1 is one or more C 1-6 ethylene optionally substituted with alkyl, C 1-6 Alkyl is one or more -OH or C 1-6 In some embodiments, L is optionally substituted with alkoxy.1 teeth, [ka] and each L is selected from the group consisting of 1 where # indicates the point of attachment to -O- and ## indicates the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0253] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0254] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is 3-10 membered heterocyclyl. In some embodiments, L 3 is a 3- to 6-membered heterocyclyl. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0255] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0256] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -NS(O)-(C 1-6 In some embodiments, R 4 is -NS(O)-(C 1-6 In some embodiments, R 4 is -NS(O)-(C 1-3 In some embodiments, R 4 teeth, [ka] is.

[0257] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R a is C 1-6 In some embodiments, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R a is C 1-3 In some embodiments, R 4 is -N(R d )2 and R d each independently represents H, C alkyl, or -S(O)-R a and R a is methyl. In some embodiments, R 4 is -NH2, and [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0258] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2 and Re each independently represents H or C 1-6 In some embodiments, R 4 is -C(O)-N(R e )2 and R e each independently represents H or C 1-3 In some embodiments, R 4 is -C(O)-N(R e )2 and R e Each of R is independently H or methyl. 4 is —C(O)—NH. In some embodiments, R 4 is —C(O)—NH(CH). In some embodiments, R 4 is —C(O)—N(CH) 2. In some variations, the embodiments provided herein also apply to compounds of formula (I′), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0259] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2 and R e is independently H or a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more oxo. 4 is -C(O)-N(R e )2 and R e is independently H or a 3- to 6-membered heterocycle, wherein the 3- to 6-membered heterocycle is optionally substituted with one or more oxo. 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0260] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached form a 3- to 10-membered heterocyclyl. In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached form a 3- to 10-membered heterocyclyl, which is a 3- to 10-membered heterocyclyl that is selected from one or more oxo, -OH, NH2, or -S(O)2-R a optionally substituted with R a is C 1-6 In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached to form a 3- to 7-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, NH-S(O)-R a , or -S(O)2-R a optionally substituted with R a is C 1-3 In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached to form a 3- to 7-membered heterocyclyl, which may be one or more of halo, oxo, -OH, NH, NH-S(O)-R a, or -S(O)2-R a optionally substituted with R a is methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0261] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is halo. In some embodiments, R 5 is Cl, or F. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0262] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0263] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is C 1-6 alkyl, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH. In some embodiments, R 5 is C 1-3 alkyl, and R 5 C 1-3 The alkyl is optionally substituted with one or more halo, or —OH. In some embodiments, R 5 is C 1-3 alkyl, and R 5 C 1-3 The alkyl is optionally substituted with one or more fluoro or —OH. In some embodiments, R 5 is methyl, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0264] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is a 3- to 10-membered heterocyclyl. In some embodiments, R 5 is a 3- to 6-membered heterocyclyl. In some embodiments, R 5 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0265] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is C 1-6 Alkoxy, C 1-6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 5 is C 1-3 Alkoxy, C 1-3 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 5 is C 1-3 Alkoxy, C 1-3 The alkoxy is optionally substituted with one or more fluoro. In some embodiments, R 5 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0266] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 6 and R 7 are each independently H or halo. In some embodiments, R 6 and R 7are each independently H or fluoro. In some embodiments, R 6 and R 7 Each of is H. In some embodiments, R 6 and R 7 One of the two is H and the other is R 6 and R 7 and the other is fluoro. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0267] In some embodiments, provided herein is a compound of Formula (I), (IA), (I-A2), or (IB) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-B3): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, 5 is independently, at each occurrence, halo, -CN, 3- to 10-membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or -OH, and 1-6 Alkoxy is optionally substituted with one or more halo; m, R 1 , R 2 , L 1 , L 3 , R 4 , R 6 , and R 7 is as defined for formula (I). In some variations, m, R in formula (I-B3) 1 , R 2 , L 1 , L 3 , R 4 , R 6 , and R7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0268] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0269] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 In some embodiments, R 2 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0270] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is 0 or 1. In some embodiments, m is 0. In some embodiments, m is 1. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0271] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0272] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0273] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is one or more C 1-6 C optionally substituted with alkyl 1-6 alkylene, C 1-6 Alkyl is -OH or C 1-6 In some embodiments, L is optionally substituted with alkoxy. 1 is methylene. In some embodiments, L 1 is one or more C 1-6 ethylene optionally substituted with alkyl, C 1-6 Alkyl is one or more -OH or C 1-6 In some embodiments, L is optionally substituted with alkoxy. 1 teeth, [ka] and each L is selected from the group consisting of 1 where # indicates the point of attachment to -O- and ## indicates the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0274] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0275] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 In some embodiments, L is alkylene. 3 is C 1-3 In some embodiments, L is alkylene. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0276] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is 3-10 membered heterocyclyl. In some embodiments, L 3 is a 3- to 6-membered heterocyclyl. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0277] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-Ra and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0278] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -N(R d )2 and R d each independently represents C alkyl, or -S(O)-R a and R a is C 1-6 In some embodiments, R 4 is -N(R d )2 and R d each independently represents C alkyl, or -S(O)-R a and R a is C 1-3 In some embodiments, R 4 is -N(R d )2 and R d Each of -S(O)2-R a and R ais methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0279] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached form a 3- to 10-membered heterocyclyl, which is optionally substituted with one or more oxo. In some embodiments, R 4 is -C(O)-N(R e )2, and both R e together with the N to which they are attached form a 3- to 7-membered heterocyclyl, which is optionally substituted with one or more oxo. 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0280] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IB), or (I-B3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 are, independently in each occurrence, halo and C 1-6 In some embodiments, R 5 are, independently in each occurrence, halo and C 1-3 In some embodiments, R 5 is independently selected at each occurrence from the group consisting of F and methyl. In some embodiments, each R 5 is F. In some embodiments, each R 5 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0281] In some embodiments, provided herein is a compound of Formula (I), (IA), or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (IC): [ka]

[0282] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , L 3 , R 4 , and R 5 are as defined for formula (I). In some variations, m, p, R of formula (IC) 1 , R 2 , R 3 , L 1 , L3 , R 4 , and R 5 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0283] In some embodiments, provided herein is a compound of Formula (I), (IA), (I-A2), or (IC) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-C1): [ka]

[0284] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, R 1 , R 2 , R 3 , L 1 , L 3 , and R 4 is as defined for formula (I). In some variations, m, R of formula (I-D) 1 , R 2 , R 3 , L 1 , L 3 , and R 4 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0285] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0286] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 1. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0287] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0288] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0289] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is C 1-6 In some embodiments, L is alkylene. 1 is ethylene. In some embodiments, L 1 teeth, [ka] where # indicates the point of attachment to -O- and ## indicates the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0290] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0291] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 In some embodiments, L is alkylene. 3 is C 1-3 In some embodiments, L is alkylene. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0292] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0293] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 3-10 is cycloalkyl. R 4 is -S(O)2-R a and R a is C 3-10 is cycloalkyl, and R a C 3-10 Cycloalkyl is one or more C 1-6 optionally substituted with alkyl, C 1-6 The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 is -S(O)2-R a and R a is C 3-6 is cycloalkyl, and R a C 3-6 Cycloalkyl is one or more C 1-6 optionally substituted with alkyl, C 1-6 The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 is -S(O)2-R a and R a is C 3-6 is cycloalkyl, and R a C 3-6 Cycloalkyl is one or more C 1-3 optionally substituted with alkyl, C 1-3 The alkyl is optionally substituted with one or more —OH. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0294] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is a 3- to 10-membered heterocyclyl. In some embodiments, R 4 is -S(O)2-R a and R a is a 3- to 10-membered heterocyclyl, and R a The 3- to 10-membered heterocyclyl may have one or more C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is a 3- to 6-membered heterocyclyl, and R a The 3- to 6-membered heterocyclyl may have one or more C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is a 3- to 6-membered heterocyclyl, and R a The 3- to 6-membered heterocyclyl may have one or more C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0295] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2 and R e each independently represents H or C 1-6 In some embodiments, R 4 is -C(O)-N(R e )2 and R e each independently represents H or C 1-3 In some embodiments, R 4 is -C(O)-N(R e )2 and R e Each of R is independently H or methyl. 4 is —C(O)—NH. In some embodiments, R 4 is —C(O)—N(CH). In some embodiments, R 4 is —C(O)—NH. In some embodiments, R 4 is -C(O)-NH(CH). In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0296] In some embodiments, provided herein is a compound of Formula (I), (IA), or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-C2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, 5 -halo, -CN, 3-10 membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or -OH, and 1-6 Alkoxy is optionally substituted with one or more halo; m, p, R 1 , R 2 , R 3 , L 1 , L 3 , and R 4 is as defined for formula (I). In some variations, R 5 -halo, -CN, 3-10 membered heterocyclyl, C 1-6 Alkyl, or C 1-6 is alkoxy, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo, or —OH, and R 5 C 1-6 Alkoxy is optionally substituted with one or more halo; m, p, R of formula (I-C2) 1 , R 2 , R 3 , L 1 , L 3 , and R 4 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0297] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0298] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 1. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0299] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0300] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0301] In some embodiments of a compound of Formula (I'), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is C 1-6 alkyl, and R 1 C 1-6 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is C 1-3 alkyl, and R 1 C 1-3 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is methyl and R 1 The methyl in R is optionally substituted with one or more F. In some embodiments, R 1 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0302] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is C 1-6 In some embodiments, L is alkylene. 1 is ethylene. In some embodiments, L 1 teeth, [ka] where # indicates the point of attachment to -O- and ## indicates the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0303] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0304] In some embodiments of a compound of Formula (I'), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 In some embodiments, L is optionally substituted with alkyl. 3 is C 1-3 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 In some embodiments, L is optionally substituted with alkyl. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0305] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I'), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 optionally substituted with alkyl, C 1-6 The alkyl is optionally substituted with one or more —OH. In some embodiments, L 3 is C 1-3 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-3 optionally substituted with alkyl, C 1-3 The alkyl is optionally substituted with one or more —OH. In some embodiments, L 3 teeth, [ka] is selected from the group consisting of:

[0306] In some embodiments of a compound of Formula (I'), (I), (IA), (I-A2), (IB), or (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 3-10 is cycloalkyl, and L 3 C 3-10 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 is C 3-8is cycloalkyl, and L 3 C 3-8 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0307] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I'), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is one or more -OH or C 1-6 In some embodiments, L is a 3- to 10-membered heterocyclyl optionally substituted with alkyl. 3 is one or more -OH or C 1-3 In some embodiments, L is a 3- to 6-membered heterocyclyl optionally substituted with alkyl. 3 teeth, [ka] is.

[0308] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-3 In some embodiments, R4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0309] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -(CH2) q OH, and q is an integer of 0 to 6. 4 is -(CH2) q OH and q is an integer from 0 to 2. In some embodiments, R 4 is —OH. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0310] In some embodiments of a compound of Formula (I'), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-C 1-6 In some embodiments, R 4 is -C(O)-C 1-3 In some embodiments, R 4is —C(O)CH. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0311] In some embodiments of a compound of Formula (I), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is C 1-6 In some embodiments, R 5 is C 1-3 In some embodiments, R 5 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0312] In some embodiments of a compound of Formula (I'), (IA), (I-A2), (IC), or (I-C2) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is C 1-6 alkyl, and R 5 C 1-6 The alkyl is optionally substituted with one or more halo. In some embodiments, R 5 is C 1-3 alkyl, and R 5 C 1-3 The alkyl is optionally substituted with one or more halo. In some embodiments, R 5 is C 1-3 alkyl, and R 5 C 1-3 The alkyl is optionally substituted with one or more fluoro. In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0313] In some embodiments of a compound of Formula (I'), (IA), (I-A2), (IC), or (I-C2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 5 is halo. In some embodiments, R 5 is Cl, or F. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0314] In some embodiments, provided herein is a compound of Formula (I), (IA), or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (ID): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing (wherein m, p, R 1 , R 2 , R 3 , L 1 , L 3 , and R 4 are as defined for formula (I). In some variations, m, p, R of formula (I) 1 , R 2 , R 3 , L 1 , L 3, and R 4 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0315] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0316] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is a C optionally substituted with one or more deuterium atoms 1-6 In some embodiments, R 2 is a C optionally substituted with one or more deuterium atoms 1-3 In some embodiments, R 2 is methyl optionally substituted with one or more deuterium atoms. In some embodiments, R 2 teeth, [ka] is.

[0317] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 1. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0318] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0319] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is Cl or I.

[0320] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1is -CN. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0321] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is C 1-6 alkyl, and R 1 C 1-6 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is C 1-3 alkyl, and R 1 C 1-3 The alkyl is optionally substituted with one or more halo. In some embodiments, R 1 is C 1-3 alkyl, and R 1 C 1-3 The alkyl is optionally substituted with one or more F. In some embodiments, R 1 is methyl and R 1 The methyl in R is optionally substituted with one or more F. In some embodiments, R 1 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0322] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1is one or more C 1-6 C optionally substituted with alkyl 1-6 In some embodiments, L is alkylene. 1 is one or more C 1-6 In some embodiments, L is ethylene optionally substituted with alkyl. 1 teeth, [ka] and each L is selected from the group consisting of 1 where # indicates the point of attachment to -O- and ## indicates the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0323] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is absent. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0324] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is -O-. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0325] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 In some embodiments, L is alkylene. 3 is C 1-3 In some embodiments, L is alkylene. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0326] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 1-6 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 In some embodiments, L is optionally substituted with alkyl. 3 is C 1-3 alkylene, and L 3 C 1-6 Alkylene is a group consisting of one or more -OH, or C 1-6 In some embodiments, L is optionally substituted with alkyl. 3 teeth, [ka] is selected from the group consisting of:

[0327] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 3-10 In some embodiments, L is cycloalkyl. 3 is C 3-8 In some embodiments, L is cycloalkyl. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0328] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 3-10 is cycloalkyl, and L 3 C 3-10 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 is C 3-8 is cycloalkyl, and L 3 C 3-8 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0329] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is C 3-10 is cycloalkyl, and L 3 C 3-10 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 is C 3-8 is cycloalkyl, and L 3 C 3-8 The cycloalkyl is optionally substituted with one or more —OH. In some embodiments, L 3 teeth, [ka] is selected from the group consisting of:

[0330] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is 3-10 membered heterocyclyl. In some embodiments, L 3 is a 3- to 6-membered heterocyclyl. 3 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0331] In some embodiments of a compound of Formula (II), e.g., a compound of (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 3 is 3-10 membered heterocyclyl. In some embodiments, L 3 is a 3- to 6-membered heterocyclyl. 3 teeth, [ka] is selected from the group consisting of:

[0332] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -S(O)2-R a and R a is C 1-6 In some embodiments, R 4 is -S(O)2-R a and R a is C 1-3 In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0333] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -C(O)-N(R e )2 and R eEach of is H. In some embodiments, R 4 is —C(O)—NH. In some variations, the embodiments provided herein also apply to compounds of formula (I′), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0334] In some embodiments of a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is one or more C 1-6 In some embodiments, R is a 3- to 10-membered heterocyclyl optionally substituted with alkyl. 4 is one or more C 1-6 In some embodiments, R is a 3- to 6-membered heterocyclyl optionally substituted with alkyl. 4 is one or more C 1-3 In some embodiments, R is a 3- to 6-membered heterocyclyl optionally substituted with alkyl. 4 is a 3- to 6-membered heterocyclyl optionally substituted with one or more methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0335] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 teeth, [ka] is.

[0336] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is one or more C 1-6 In some embodiments, R is a 3- to 10-membered heterocyclyl optionally substituted with alkyl. 4 is one or more C 1-6 In some embodiments, R is a 3- to 6-membered heterocyclyl optionally substituted with alkyl. 4 is one or more C 1-3 In some embodiments, R is a 3- to 6-membered heterocyclyl optionally substituted with alkyl. 4 is a 3- to 6-membered heterocyclyl optionally substituted with one or more methyl. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0337] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -(CH2) q OH, and q is an integer of 0 to 6. 4 is -(CH2) q OH and q is an integer from 0 to 2. In some embodiments, R 4 is —OH. In some embodiments, R 4 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0338] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -N(R d )2 and R d Each of is independently H. In some embodiments, R 4 is -NH2. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0339] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 4 is -P(O)(C 1-6 In some embodiments, R 4 is -P(O)(C 1-3 In some embodiments, R 4 is -P(O)(CH3)2. In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0340] In some embodiments, provided herein is a compound of Formula (I), (IA) or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (IE): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein ring A is a 5- to 10-membered heterocyclyl or a 5- to 10-membered heteroaryl, and the 5- to 10-membered heterocyclyl of ring A is selected from the group consisting of one or more R b and the 5-10 membered heteroaryl of ring A is optionally substituted with one or more R c optionally substituted with m, p, R 1 , R 2 , R 3 , L 1 , X 2 , R b , R c , R 6 , and R 7 is as defined for formula (I). In some variations, ring A is a 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, and the 5-10 membered heterocyclyl of ring A is selected from the group consisting of one or more R b and the 5-10 membered heteroaryl of ring A is optionally substituted with one or more R c and m, p, R of formula (IE) are optionally substituted with 1 , R 2 , R 3 , L 1 , X 2 , R b , R c , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0341] In some embodiments, provided herein is a compound of Formula (I), (IA) or (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-E1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein ring A is a 5- to 10-membered heterocyclyl or a 5- to 10-membered heteroaryl, and the 5- to 10-membered heterocyclyl of ring A is selected from the group consisting of one or more R b and the 5-10 membered heteroaryl of ring A is optionally substituted with one or more R c optionally substituted with m, p, R 1 , R 2 , R 3 , L 1 , X 1 , R b , R c , R 6 , and R 7 is as defined for formula (I). In some variations, ring A is a 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, and the 5-10 membered heterocyclyl of ring A is selected from the group consisting of one or more R b and the 5-10 membered heteroaryl of ring A is optionally substituted with one or more R c and m, p, R of formula (I-E1) are optionally substituted with 1 , R 2 , R 3 , L 1 , X 1 , R b , R c , R 6 , and R 7 is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0342] In some embodiments, provided herein is a compound of Formula (I'), (IA), (I-A2), or (IE) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-E2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein r is an integer from 0 to 1; Y 1 and Y 2 are each independently one or more H or R b C or N optionally substituted by m, R 1 , R 2 , L 1 , X 2 , and R b is as defined for formula (I') or (II); the dashed line represents a single or double bond).

[0343] In some embodiments, provided herein is a compound of Formula (I'), (IA), (I-A2), or (IE) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-E3): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein r is an integer from 0 to 1; Y 1 and Y 2 are each independently one or more H or R b is C or N optionally substituted by b1 is OH; R b2 is H, C 1-6 Alkyl, or C 3-10 is cycloalkyl, and R b2 C 1-6 Alkyl is optionally substituted with one or more OH; m, R 1 , R 2 , L 1 , X2 , and R b is as defined for formula (I') or (II); the dashed line represents a single or double bond).

[0344] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (I-E3) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The site represented by [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0345] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (I-E3) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The site represented by [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0346] In some embodiments, provided herein is a compound of Formula (I'), (IA), (I-A2), or (IE) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-E4): [ka]

[0347] a or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein r is an integer from 0 to 1; Y 2 , Y 3 and Y 4 are each independently one or more H or R c C or N optionally substituted by m, R 1 , R 2 , L 1 , X 2 , and R c is as defined for formula (I') or (II); the dashed line represents a single or double bond).

[0348] In some embodiments, provided herein is a compound of Formula (I'), (IA), (I-A2), or (IE) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-E5): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein r is an integer from 0 to 1; Y 3 , Y 4 and Y 5 are each independently one or more H or R c is C or N optionally substituted by c1 is OH; R c2 is H, C 1-6 Alkyl, or C 3-10 is cycloalkyl, and R c2 C1-6 Alkyl is optionally substituted with one or more OH; m, R 1 , R 2 , L 1 , X 2 , and R c is as defined for formula (I') or (II); the dashed line represents a single or double bond).

[0349] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (I-E5) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The site represented by [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0350] In some embodiments of a compound of Formula (I'), (IA), (I-A2), or (IE) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The site represented by [ka] In some variations, the embodiments provided herein also apply to compounds of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0351] In some embodiments, provided herein is a compound of Formula (I), (IA) or (I-A2), (IE), or (I-E1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (IF): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein ring A is a 5- to 10-membered heterocyclyl or a 5- to 10-membered heteroaryl, and the 5- to 10-membered heterocyclyl of ring A is selected from the group consisting of one or more R b and the 5-10 membered heteroaryl of ring A is optionally substituted with one or more R c optionally substituted with m, p, R 1 , R 2 , R 3 , L 1 , R 5 , R b , and R c is as defined for formula (I). In some variations, ring A is a 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, and the 5-10 membered heterocyclyl of ring A is selected from the group consisting of one or more R b and the 5-10 membered heteroaryl of ring A is optionally substituted with one or more R c and m, p, R of formula (IF) are optionally substituted with 1 , R 2 , R 3 , L 1 , R 5 , R b , and R c is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0352] In some embodiments, provided herein is a compound of Formula (I), (IA) or (I-A2), (IE), (I-E1), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (I-F1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein ring A is a 5- to 10-membered heterocyclyl or a 5- to 10-membered heteroaryl, and the 5- to 10-membered heterocyclyl of ring A is selected from the group consisting of one or more R b and the 5-10 membered heteroaryl of ring A is optionally substituted with one or more R c optionally substituted with m, R 1 , R 2 , L 1 , R b , and R c is as defined for formula (I). In some variations, ring A is a 5-10 membered heterocyclyl or a 5-10 membered heteroaryl, and the 5-10 membered heterocyclyl of ring A is selected from the group consisting of one or more R b and the 5-10 membered heteroaryl of ring A is optionally substituted with one or more R c m, R in formula (I-F1) 1 , R 2 , L 1 , R b , and R c is as defined for a compound of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0353] In some embodiments of a compound of Formula (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2is H. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0354] In some embodiments of a compound of Formula (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, and R 2 C 1-6 Alkyl is one or more -OH, -NH2, or C 1-6 In some embodiments, R 2 is methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0355] In some embodiments of a compound of Formula (II), e.g., a compound of Formula (I′), (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, and R 2 C 1-6 Alkyl is a group that contains one or more deuterium, -OH, -NH2, or C 1-6 In some embodiments, R 2 is methyl optionally substituted with one or more deuterium atoms. In some embodiments, R 2 teeth, [ka] is.

[0356] In some embodiments of a compound of Formula (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 3-10 is cycloalkyl, and R 2 C 3-10 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R 2 is C 3-6 is cycloalkyl, and R 2 C 3-6 The cycloalkyl is optionally substituted with one or more -OH. In some embodiments, R 2 teeth, [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0357] In some embodiments of a compound of Formula (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, m is an integer from 0 to 4. In some embodiments, m is an integer from 0 to 2. In some embodiments, m is 0 or 1. In some embodiments, m is 0. In some embodiments, m is 1. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0358] In some embodiments of a compound of Formula (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is halo. In some embodiments, R 1 is Cl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0359] In some embodiments of a compound of Formula (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is -CN. In some variations, the embodiments provided herein also apply to a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In some embodiments of a compound of formula (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is C 1-6 alkylene, and L 1 C 1-6 Alkylene is one or more C 1-6 In some embodiments, L is optionally substituted with alkyl. 1 is ethylene, and L 1 Ethylene has one or more C 1-6 In some embodiments, L is optionally substituted with alkyl. 1 teeth, [ka] and each L is selected from the group consisting of1 where # indicates the point of attachment to -O- and ## indicates the point of attachment to the rest of the molecule. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0360] In some embodiments of a compound of Formula (I), (IA) or (I-A2), (IE), (I-E1), (IF), or (I-F1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is selected from the group consisting of R b and optionally substituted with one or more of R b In some embodiments, ring A is a 5-10 membered heterocyclyl, wherein the 5-10 membered heterocyclyl is R b ...

Claims

1. A compound of formula (II): 【Chemical 1299】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 , if present, is independently selected at each occurrence from the group consisting of halo, —CN, C 1-6 alkoxy, and C 1-6 alkyl; said C 1-6 alkoxy for R 1 is optionally substituted with one or more halo; said C 1-6 alkyl of R 1 is optionally substituted with one or more halo; R 2 is H, C 1-6 alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; said C 1-6 alkyl of R 2 is optionally substituted with one or more deuterium, halo, —OH, —NH 2 , or C 1-6 alkoxy; said C 3-10 cycloalkyl of R 2 is optionally substituted with one or more —OH; R 3 , if present, is C 1-6 alkyl; L 1 is C 1-6 alkylene; said C 1-6 alkylene of L 1 is optionally substituted with one or more deuterium atoms or C 1-6 alkyl; said C 1-6 alkyl optionally further substituted with one or more —OH or C 1-6 alkoxy; L 2 is O or N(R x ), where R x is H or C 1-6 alkyl; (1) L 3 is absent or is O, C 3-10 cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 alkylene; said C 3-10 cycloalkyl of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkylene of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkyl is optionally substituted with one or more —OH; said 3- to 10-membered heterocyclyl of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; X 1 and X 2 are each independently N or C(R 5 ); R 4 is (i)-S(O) 2 -R a ; (ii) 5- to 20-membered heteroaryl, wherein said 5- to 20-membered heteroaryl of R 4 is optionally substituted with one or more C 1-6 alkyl; (iii) —N(R d ) 2 , where R d is independently for each occurrence H, C 1-6 alkyl, or —S(O) 2 —R a ; The C 1-6 alkyl of R d is optionally substituted with one or more —OH; (iv) -NS(O)-(Ci_6 alkyl) 2 , wherein said Ci_6 alkyl is optionally substituted with one or more -OH; (v) —C(O)—N(R e ) 2 , where R e is independently for each occurrence H, C 1-6 alkyl, or a 3- to 10-membered heterocycle; said 3- to 10-membered heterocycle of R e is optionally substituted with one or more oxo, or both R e together with the N to which they are attached join to form a 3- to 10-membered heterocyclyl; said 3- to 10-membered heterocyclyl optionally substituted with one or more halo, oxo, —OH, NH 2 , —NH—S(O) 2 —R a , or —S(O) 2 —R a ; (vi) 3- to 10-membered heterocyclyl optionally substituted with one or more C 1-6 alkyl, —OH, oxo, or —S(O) 2 —R a ; (vii) —S(O)—N(C 1-6 alkyl)-(C 1-6 alkyl), (viii)-CN, (ix) —(CH 2 ) q OH, where q is an integer from 0 to 6; (x)—C(O)—C 1-6 alkyl, or (xi) -P(O)(C 1-6 alkyl) 2 ; or (2) L 3 is absent; one of X 1 and X 2 is N or C(R 5 ); the other of X 1 and X 2 is N or C which, together with R 4 and the atom to which they are attached, form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; said 5- to 10-membered heterocyclyl is optionally substituted with one or more R b ; R b is independently at each occurrence selected from the group consisting of —OH, halo, oxo, C 1-6 alkyl, —C(O)—C 1-6 alkyl, —C(O)—NH 2 , —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , —S(O) 2 —R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; said C 1-6 alkyl of R b is optionally substituted with one or more halo, OH, —S(O) 2 —C 1-6 alkyl, or C 3-10 cycloalkyl; said C 3-10 cycloalkyl of said C 1-6 alkyl of R b is optionally further substituted with one or more C 1-6 alkyl or —OH; said C 3-10 cycloalkyl of R b is optionally substituted with one or more —OH, C 3-10 cycloalkyl, or C 1-6 alkyl; said C 1-6 alkyl of said C 3-10 cycloalkyl of R b is optionally further substituted with one or more —OH, deuterium, or halo; said 5- to 20-membered heteroaryl is optionally substituted with one or more R c ; R c at each occurrence is independently selected from the group consisting of halo, C 1-6 alkyl, —C(O)—C 1-6 alkyl, —C(O)—NH 2 , —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , —S(O) 2 —R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; said C 1-6 alkyl of R c is optionally substituted with one or more —S(O) 2 —C 1-6 alkyl; said C 3-10 cycloalkyl of R c is optionally substituted with one or more —OH or C 1-6 alkyl; said 3- to 10-membered heterocyclyl of R c is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkyl of said 3 to 10 membered heterocyclyl of R c is optionally further substituted with one or more —OH; Either R a is independently at each occurrence: (i) C 1-6 alkyl optionally substituted with one or more halo, —OH, —S(O) 2 —C 1-6 alkyl, or —N(C 1-6 alkyl)-C(O)—C 1-6 alkyl; (ii) C 3-10 cycloalkyl optionally substituted with one or more —OH, —C(O) 2 —C 1-6 alkyl, —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , or —C(O)—C 3-10 heterocyclyl, or C 1-6 alkyl; the C 1-6 alkyl is optionally substituted with one or more —OH; (iii) a 3- to 10-membered heterocyclyl optionally substituted with one or more C 1-6 alkyls, or (iv) NH(C 1-6 alkyl); R 5 is independently at each occurrence H, halo, —CN, 3- to 10-membered heterocyclyl, C 1-6 alkyl, or C 1-6 alkoxy; said C 1-6 alkyl of R 5 is optionally substituted with one or more halo or —OH; said C 1-6 alkoxy of R 5 is optionally substituted with one or more halo; X 3 is N or C(R 6 ); X 4 is N or C(R 7 ); R 6 and R 7 are each independently H or halo.

2. L 2 is O, whereby the compound is a compound of formula (IA): 【Chemical 1302】 2. The compound of claim 1, which is:

3. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein n is 1 or 2.

4. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 2 is H, C 1-3 alkyl, C 3-6 cycloalkyl, or 3- to 10-membered heterocyclyl, and the C 1-3 alkyl of R 2 is optionally substituted with one or more deuterium, halo, -OH, -NH 2 , or C 1-3 alkoxy, and the C 3-6 cycloalkyl of R 2 is optionally substituted with one or more -OH.

5. The compound of claim 1, wherein m is 0, 1, or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

6. R 1 is halo, —CN, —C 1-3 alkoxy, or —C 1-3 alkyl; said C 1-3 alkoxy for R 1 is optionally substituted with one or more halo; said C 1-3 alkyl of R 1 is optionally substituted with one or more halo; 10. A compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

7. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein p is 0 or 1.

8. L 1 is 【Chemical 1303】 and for each L 1 , * indicates the point of attachment to L 2 and ** indicates the point of attachment to the rest of the molecule, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

9. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L 3 is absent.

10. L 3 is —O—, C 3-10 cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 alkylene; said C 3-10 cycloalkyl of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkylene of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkyl is optionally substituted with one or more —OH; said 3- to 10-membered heterocyclyl of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; 10. A compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

11. L 3 is —O—, 【Chemical 1304】 11. The compound of claim 10, selected from the group consisting of: or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

12. R 4 is S(O) 2 -R a , 5- to 10-membered heteroaryl, -N(R d ) 2 , -NS(O)-(C 1-3 alkyl) 2 , -C(O)-N(R e ) 2 , 3- to 6-membered heterocyclyl, -S(O)(N-C 1-3 alkyl)-(C 1-3 alkyl), -CN, -OH, -C(O)-C 1-3 alkyl, or -P(O)(C 1-3 alkyl) 2 ; said 5- to 20-membered heteroaryl of R 4 is optionally substituted with one or more C 1-3 alkyl; said 3- to 6-membered heterocyclyl of R 4 is optionally substituted with one or more -OH, oxo, C 1-3 alkyl, or -S(O) 2 -R a ; 10. A compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

13. The compound of claim 12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R e is independently for each occurrence H, C 1-6 alkyl, or a 3- to 10-membered heterocycle, wherein said 3- to 10-membered heterocycle is optionally substituted with one or more oxo.

14. The compound of claim 12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein both R e s together with the N to which they are attached form a 3- to 10-membered heterocyclyl, said 3- to 10-membered heterocyclyl optionally substituted with one or more halo, oxo, -OH, -NH 2 , -NH-S(O) 2 -R a , or -S(O) 2 -R a , wherein R a is C 1-6 alkyl.

15. The compound of claim 1, wherein each of X 1 and X 2 is C(R 5 ), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

16. The compound of claim 1, wherein each of X 1 and X 2 is N, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

17. The compound of claim 1, wherein one of X 1 and X 2 is N and the other is C(R 5 ), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

18. The compound of claim 1, wherein one of X 1 and X 2 is N or CR 5 , and the other of X 1 and X 2 is N or C which, together with R 4 and the atoms to which they are attached, form a 5- to 10-membered heterocyclyl optionally substituted with one or more R b , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

19. The compound of claim 1, wherein one of X 1 and X 2 is N or CR 5 , and the other of X 1 and X 2 is N or C which, together with R 4 and the atoms to which they are attached, form a 5- to 10-membered heteroaryl optionally substituted with one or more R c , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

20. The compound comprising: 【Chemical 1311-1】 【Chemical Engineering 1311-2】 【Chemical 1311-3】 【Chemical 1311-4】 【Chemical 1311-5】 【Chemical 1311-6】 【Chemical 1311-7】 【Chemical 1311-8】 【Chemical 1311-9】 【Chemical 1311-10】 【Chemistry 1311-11】 【Chemistry 1311-12】 【Chemistry 1311-13】 【Chemistry 1311-14】 【Chemistry 1311-15】 【Chemical Engineering 1311-16】 【Chemistry 1311-17】 【Chemistry 1311-18】 【Chemistry 1311-19】 【Chemical 1311-20】 【Chemistry 1311-21】 【Chemistry 1311-22】 【Chemistry 1311-23】 【Chemistry 1311-24】 【Chemistry 1311-25】 or a pharmaceutically acceptable salt of any of the foregoing, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

21. A process for preparing a compound of formula (II) according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, said process comprising reacting a compound of formula (II'-A): 【Chemical 1305】 (In the formula, m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 , if present, is independently selected at each occurrence from the group consisting of halo, —CN, C 1-6 alkoxy, and C 1-6 alkyl; said C 1-6 alkoxy for R 1 is optionally substituted with one or more halo; said C 1-6 alkyl of R 1 is optionally substituted with one or more halo; R 2 is H, C 1-6 alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; said C 1-6 alkyl of R 2 is optionally substituted with one or more deuterium, halo, —OH, —NH 2 , or C 1-6 alkoxy; said C 3-10 cycloalkyl of R 2 is optionally substituted with one or more —OH; and R 3 , if present, is C 1-6 alkyl. of, Compound of formula (II'-B): 【Chemical 1306】 (In the formula, The dashed lines represent single or double bonds; Y 1 is halo, oxo, or a sulfonate ester; L 1 is C 1-6 alkylene; said C 1-6 alkylene of L 1 is optionally substituted with one or more deuterium atoms or C 1-6 alkyl; said C 1-6 alkyl optionally further substituted with one or more —OH or C 1-6 alkoxy; L 2 is O or N(R x ), where R x is H or C 1-6 alkyl; (1) L 3 is absent or is O, C 3-10 cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 alkylene; said C 3-10 cycloalkyl of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkylene of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkyl is optionally substituted with one or more —OH; said 3- to 10-membered heterocyclyl of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; X 1 and X 2 are each independently N or C(R 5 ); R 4 is (i)-S(O) 2 -R a ; (ii) 5- to 20-membered heteroaryl, wherein said 5- to 20-membered heteroaryl of R 4 is optionally substituted with one or more C 1-6 alkyl; (iii) —N(R d ) 2 , where R d is independently for each occurrence H, C 1-6 alkyl, or —S(O) 2 —R a ; The C 1-6 alkyl of R d is optionally substituted with one or more —OH; (iv) -NS(O)-(Ci_6 alkyl) 2 , wherein said Ci_6 alkyl is optionally substituted with one or more -OH; (v) —C(O)—N(R e ) 2 , where R e is independently for each occurrence H, C 1-6 alkyl, or a 3- to 10-membered heterocycle; said 3- to 10-membered heterocycle of R e is optionally substituted with one or more oxo, or both R e together with the N to which they are attached join to form a 3- to 10-membered heterocyclyl; said 3- to 10-membered heterocyclyl optionally substituted with one or more halo, oxo, —OH, NH 2 , —NH—S(O) 2 —R a , or —S(O) 2 —R a ; (vi) 3- to 10-membered heterocyclyl optionally substituted with one or more C 1-6 alkyl, —OH, oxo, or —S(O) 2 —R a ; (vii) —S(O)—N(C 1-6 alkyl)-(C 1-6 alkyl), (viii)-CN, (ix) —(CH 2 ) q OH, where q is an integer from 0 to 6; (x)—C(O)—C 1-6 alkyl, or (xi) -P(O)(C 1-6 alkyl) 2 ; or (2) L 3 is absent; one of X 1 and X 2 is N or C(R 5 ); the other of X 1 and X 2 is N or C which, together with R 4 and the atom to which they are attached, form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; said 5- to 10-membered heterocyclyl is optionally substituted with one or more R b ; R b is independently at each occurrence selected from the group consisting of —OH, halo, oxo, C 1-6 alkyl, —C(O)—C 1-6 alkyl, —C(O)—NH 2 , —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , —S(O) 2 —R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; said C 1-6 alkyl of R b is optionally substituted with one or more halo, OH, —S(O) 2 —C 1-6 alkyl, or C 3-10 cycloalkyl; said C 3-10 cycloalkyl of said C 1-6 alkyl of R b is optionally further substituted with one or more C 1-6 alkyl or —OH; said C 3-10 cycloalkyl of R b is optionally substituted with one or more —OH, C 3-10 cycloalkyl, or C 1-6 alkyl; said C 1-6 alkyl of said C 3-10 cycloalkyl of R b is optionally further substituted with one or more —OH, deuterium, or halo; said 5- to 20-membered heteroaryl is optionally substituted with one or more R c ; R c at each occurrence is independently selected from the group consisting of halo, C 1-6 alkyl, —C(O)—C 1-6 alkyl, —C(O)—NH 2 , —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , —S(O) 2 —R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; said C 1-6 alkyl of R c is optionally substituted with one or more —S(O) 2 —C 1-6 alkyl; said C 3-10 cycloalkyl of R c is optionally substituted with one or more —OH or C 1-6 alkyl; said 3- to 10-membered heterocyclyl of R c is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkyl of said 3 to 10 membered heterocyclyl of R c is optionally further substituted with one or more —OH; Either R a is independently at each occurrence: (i) C 1-6 alkyl optionally substituted with one or more halo, —OH, —S(O) 2 —C 1-6 alkyl, or —N(C 1-6 alkyl)-C(O)—C 1-6 alkyl; (ii) C 3-10 cycloalkyl optionally substituted with one or more —OH, —C(O) 2 —C 1-6 alkyl, —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , or —C(O)—C 3-10 heterocyclyl, or C 1-6 alkyl; the C 1-6 alkyl is optionally substituted with one or more —OH; (iii) a 3- to 10-membered heterocyclyl optionally substituted with one or more C 1-6 alkyls, or (iv) NH(C 1-6 alkyl); R 5 is independently at each occurrence H, halo, —CN, 3- to 10-membered heterocyclyl, C 1-6 alkyl, or C 1-6 alkoxy; said C 1-6 alkyl of R 5 is optionally substituted with one or more halo or —OH; said C 1-6 alkoxy of R 5 is optionally substituted with one or more halo; X 3 is N or C(R 6 ); X 4 is N or C(R 7 ); R 6 and R 7 are each independently H or halo. to obtain a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

22. A process for preparing a compound of formula (II) according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, comprising reacting a compound of formula (II'-C): 【Chemical 1307】 (In the formula, m is an integer from 0 to 4; n is an integer from 0 to 2; p is an integer from 0 to 10; R 1 , if present, is independently selected at each occurrence from the group consisting of halo, —CN, C 1-6 alkoxy, and C 1-6 alkyl; said C 1-6 alkoxy for R 1 is optionally substituted with one or more halo; said C 1-6 alkyl of R 1 is optionally substituted with one or more halo; R 2 is H, C 1-6 alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; said C 1-6 alkyl of R 2 is optionally substituted with one or more deuterium, halo, —OH, —NH 2 , or C 1-6 alkoxy; said C 3-10 cycloalkyl of R 2 is optionally substituted with one or more —OH; R 3 , if present, is C 1-6 alkyl; L 1 is C 1-6 alkylene; said C 1-6 alkylene of L 1 is optionally substituted with one or more deuterium atoms or C 1-6 alkyl; said C 1-6 alkyl optionally further substituted with one or more —OH or C 1-6 alkoxy; Y 2 is halo, —OH or —NH 2 . of, Compound of formula (II'-D): 【Chemical 1308】 (In the formula, Y 3 is —OH or —NH(R x ), where each R x is independently H or C 1-6 alkyl; (1) L 3 is absent or is O, C 3-10 cycloalkyl, 3- to 10-membered heterocyclyl, or C 1-6 alkylene; said C 3-10 cycloalkyl of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkylene of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkyl is optionally substituted with one or more —OH; said 3- to 10-membered heterocyclyl of L 3 is optionally substituted with one or more —OH or C 1-6 alkyl; X 1 and X 2 are each independently N or C(R 5 ); R 4 is (i)-S(O) 2 -R a ; (ii) 5- to 20-membered heteroaryl, wherein said 5- to 20-membered heteroaryl of R 4 is optionally substituted with one or more C 1-6 alkyl; (iii) —N(R d ) 2 , where R d is independently for each occurrence H, C 1-6 alkyl, or —S(O) 2 —R a ; The C 1-6 alkyl of R d is optionally substituted with one or more —OH; (iv) -NS(O)-(Ci_6 alkyl) 2 , wherein said Ci_6 alkyl is optionally substituted with one or more -OH; (v) —C(O)—N(R e ) 2 , where R e is independently for each occurrence H, C 1-6 alkyl, or a 3- to 10-membered heterocycle; said 3- to 10-membered heterocycle of R e is optionally substituted with one or more oxo, or both R e together with the N to which they are attached join to form a 3- to 10-membered heterocyclyl; said 3- to 10-membered heterocyclyl optionally substituted with one or more halo, oxo, —OH, NH 2 , —NH—S(O) 2 —R a , or —S(O) 2 —R a ; (vi) 3- to 10-membered heterocyclyl optionally substituted with one or more C 1-6 alkyl, —OH, oxo, or —S(O) 2 —R a ; (vii) —S(O)—N(C 1-6 alkyl)-(C 1-6 alkyl), (viii)-CN, (ix) —(CH 2 ) q OH, where q is an integer from 0 to 6; (x)—C(O)—C 1-6 alkyl, or (xi) -P(O)(C 1-6 alkyl) 2 ; or (2) L 3 is absent; one of X 1 and X 2 is N or C(R 5 ); the other of X 1 and X 2 is N or C which, together with R 4 and the atom to which they are attached, form a 5- to 10-membered heterocyclyl or a 5- to 20-membered heteroaryl; said 5- to 10-membered heterocyclyl is optionally substituted with one or more R b ; R b is independently at each occurrence selected from the group consisting of —OH, halo, oxo, C 1-6 alkyl, —C(O)—C 1-6 alkyl, —C(O)—NH 2 , —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , —S(O) 2 —R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; said C 1-6 alkyl of R b is optionally substituted with one or more halo, OH, —S(O) 2 —C 1-6 alkyl, or C 3-10 cycloalkyl; said C 3-10 cycloalkyl of said C 1-6 alkyl of R b is optionally further substituted with one or more C 1-6 alkyl or —OH; said C 3-10 cycloalkyl of R b is optionally substituted with one or more —OH, C 3-10 cycloalkyl, or C 1-6 alkyl; said C 1-6 alkyl of said C 3-10 cycloalkyl of R b is optionally further substituted with one or more —OH, deuterium, or halo; said 5- to 20-membered heteroaryl is optionally substituted with one or more R c ; R c at each occurrence is independently selected from the group consisting of halo, C 1-6 alkyl, —C(O)—C 1-6 alkyl, —C(O)—NH 2 , —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , —S(O) 2 —R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; said C 1-6 alkyl of R c is optionally substituted with one or more —S(O) 2 —C 1-6 alkyl; said C 3-10 cycloalkyl of R c is optionally substituted with one or more —OH or C 1-6 alkyl; said 3- to 10-membered heterocyclyl of R c is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkyl of said 3 to 10 membered heterocyclyl of R c is optionally further substituted with one or more —OH; Either R a is independently at each occurrence: (i) C 1-6 alkyl optionally substituted with one or more halo, —OH, —S(O) 2 —C 1-6 alkyl, or —N(C 1-6 alkyl)-C(O)—C 1-6 alkyl; (ii) C 3-10 cycloalkyl optionally substituted with one or more —OH, —C(O) 2 —C 1-6 alkyl, —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , or —C(O)—C 3-10 heterocyclyl, or C 1-6 alkyl; the C 1-6 alkyl is optionally substituted with one or more —OH; (iii) a 3- to 10-membered heterocyclyl optionally substituted with one or more C 1-6 alkyls, or (iv) NH(C 1-6 alkyl); R 5 is independently at each occurrence H, halo, —CN, 3- to 10-membered heterocyclyl, C 1-6 alkyl, or C 1-6 alkoxy; said C 1-6 alkyl of R 5 is optionally substituted with one or more halo or —OH; said C 1-6 alkoxy of R 5 is optionally substituted with one or more halo; X 3 is N or C(R 6 ); X 4 is N or C(R 7 ); R 6 and R 7 are each independently H or halo. to obtain a compound of formula (II), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

23. A pharmaceutical composition comprising (i) a compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.

24. A composition for use in a method for inhibiting APOL1 in a cell, the composition comprising: a) a compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; b) A pharmaceutical composition comprising (i) a compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. Including, The composition, wherein the method comprises exposing the cell to the composition.

25. A composition for treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof, comprising: a) a compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; b) A pharmaceutical composition comprising (i) a compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients. Including, The composition, wherein the disease, disorder, or condition is selected from the group consisting of chronic kidney disease, focal segmental glomerulosclerosis (FSGS), kidney disease caused by hypertension, human immunodeficiency virus-associated nephropathy (HIVAN), sickle cell nephropathy, lupus nephritis, diabetic kidney disease, APOL1-associated nephropathy, viral nephropathy, COVID-19-associated nephropathy, preeclampsia, and sepsis. (i) a compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising a compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use in treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof. A kit comprising: The kit, wherein the disease, disorder, or condition is selected from the group consisting of chronic kidney disease (CKD), focal segmental glomerulosclerosis (FSGS), kidney disease caused by hypertension, human immunodeficiency virus-associated nephropathy (HIVAN), sickle cell nephropathy, lupus nephritis, diabetic kidney disease, APOL1-associated nephropathy, viral nephropathy, COVID-19-associated nephropathy, preeclampsia, and sepsis.

27. The compound of claim 27, wherein the compound is a compound of formula (II-A): 【Chemistry 11】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Ring A is a 5- to 10-membered heterocyclyl or a 5- to 10-membered heteroaryl; said 5- to 10-membered heterocyclyl of Ring A is optionally substituted with one or more R b ; 2. The compound of claim 1, wherein said 5-10 membered heteroaryl of Ring A is optionally substituted with one or more R c , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

28. The compound comprising: 【Chemical 1312-1】 【Chemistry 1312-2】 or a pharmaceutically acceptable salt of any of the foregoing, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

29. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemical 1313】 or a pharmaceutically acceptable salt thereof.

30. Structure 【Chemistry 1314】 The compound 5-chloro-1'-[2-({2-oxo-1-[(trans)-3-hydroxycyclobutyl]-1,2,3,4-tetrahydroquinolin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

31. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemical 1315】 or a pharmaceutically acceptable salt thereof.

32. Structure 【Chemistry 1316】 The compound 5-chloro-1'-[2-({3-methyl-2-oxo-1H,2H,3H-imidazo[4,5-b]pyridin-6-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

33. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1317】 or a pharmaceutically acceptable salt thereof.

34. Structure 【Chemical 1318】 The compound 4-(2-{5-chloro-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-1'-yl}ethoxy)-2-(difluoromethyl)benzamide having the formula:

35. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1319】 or a pharmaceutically acceptable salt thereof.

36. Structure 【Chemistry 1320】 1. The compound 1'-{2-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]ethyl}-1-methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile, having the formula:

37. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1321】 or a pharmaceutically acceptable salt thereof.

38. Structure 【Chemistry 1322】 1. The compound 2-[4-(2-{5-cyano-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-1'-yl}ethoxy)phenyl]-2-methylpropanamide, having the formula:

39. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemical 1323】 or a pharmaceutically acceptable salt thereof.

40. Structure 【Chemistry 1324】 The compound 1'-{2-[4-(1,1-dioxo-1λ 6 -thiomorpholine-4-carbonyl)-3-(trifluoromethyl)phenoxy]ethyl}-1-methyl-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile having the formula:

41. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemical 1325】 or a pharmaceutically acceptable salt thereof.

42. Structure 【Chemistry 1326】 1. The compound 1'-{1-[4-(3-methanesulfonyloxetan-3-yl)phenoxy]propan-2-yl}-2-oxo-1,2-dihydrospiro[indole-3,4'-piperidine]-5-carbonitrile, having the formula:

43. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1327】 or a pharmaceutically acceptable salt thereof.

44. Structure 【Chemical 1328】 The compound 5-chloro-1'-[2-(3-fluoro-4-{6-methanesulfonyl-2,6-diazaspiro[3.3]heptane-2-carbonyl}phenoxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

45. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1329】 or a pharmaceutically acceptable salt thereof.

46. Structure 【Chemistry 1330】 1. The compound, 5-(difluoromethyl)-1′-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4′-piperidin]-2-one, having the formula:

47. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1331】 or a pharmaceutically acceptable salt thereof.

48. Structure 【Chemistry 1332】 1. The compound 5-chloro-1′-[2-({7-oxo-8-[(cis)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4′-piperidin]-2-one, having the formula:

49. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemical 1333】 or a pharmaceutically acceptable salt thereof.

50. Structure 【Chemistry 1334】 The compound 5-chloro-1'-(2-{[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

51. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1335】 or a pharmaceutically acceptable salt thereof.

52. Structure 【Chemical 1336】 The compound, 5-chloro-1'-[2-({7-oxo-8-[(trans)-3-hydroxy-3-methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

53. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1337】 or a pharmaceutically acceptable salt thereof.

54. Structure 【Chemical 1338】 The compound 5-chloro-1'-(2-{[8-(3-hydroxyazetidin-1-yl)-1,7-naphthyridin-3-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

55. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1339】 or a pharmaceutically acceptable salt thereof.

56. Structure 【Chemistry 1340】 1. The compound 5-chloro-1′-[2-({7-oxo-8-[(cis)-3-ethyl-3-hydroxycyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4′-piperidin]-2-one, having the formula:

57. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1341】 or a pharmaceutically acceptable salt thereof.

58. Structure 【Chemistry 1342】 The compound, 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

59. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1343】 or a pharmaceutically acceptable salt thereof.

60. Structure 【Chemical 1344】 The compound, 5-chloro-1'-[2-({7-oxo-8-[(cis)-3-hydroxy-3-( 2 H 3 )methylcyclobutyl]-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

61. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1345】 or a pharmaceutically acceptable salt thereof.

62. Structure 【Chemistry 1346】 The compound, 5-chloro-1'-[2-({1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-indazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

63. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1347】 or a pharmaceutically acceptable salt thereof.

64. Structure 【Chemical 1348】 The compound, 5-chloro-1'-[2-({2-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

65. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1349】 or a pharmaceutically acceptable salt thereof.

66. Structure [Chemical 1350] The compound, 5-chloro-1'-[2-({2-oxo-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-2,3-dihydro-1H-1,3-benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

67. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1351】 or a pharmaceutically acceptable salt thereof.

68. Structure 【Chemistry 1352】 The compound 5-chloro-1'-(2-{[2-(1-methanesulfonylcyclopropyl)pyrimidin-5-yl]oxy}ethyl)-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

69. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1353】 or a pharmaceutically acceptable salt thereof.

70. Structure 【Chemistry 1354】 The compound, 5-chloro-1'-[2-({2-methyl-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-7-(trifluoromethyl)-1H-1,3-benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

71. A compound, or a pharmaceutically acceptable salt thereof, comprising: structure 【Chemistry 1355】 or a pharmaceutically acceptable salt thereof.

72. Structure 【Chemistry 1356】 The compound, 5-chloro-1'-[2-({7-fluoro-1-[(cis)-3-hydroxy-3-methylcyclobutyl]-1H-1,3-benzodiazol-5-yl}oxy)ethyl]-1,2-dihydrospiro[indole-3,4'-piperidin]-2-one, having the formula:

73. The compound of claim 73, wherein the compound is a compound of formula (IE): 【Chemical 1358】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Ring A is a 5- to 10-membered heterocyclyl or a 5- to 10-membered heteroaryl; said 5- to 10-membered heterocyclyl of Ring A is optionally substituted with one or more R b ; said 5-10 membered heteroaryl of Ring A is optionally substituted with one or more R c ; m is an integer from 0 to 4; p is an integer from 0 to 10; R 1 , if present, is independently selected at each occurrence from the group consisting of halo, —CN, C 1-6 alkoxy, and C 1-6 alkyl; said C 1-6 alkoxy for R 1 is optionally substituted with one or more halo; said C 1-6 alkyl of R 1 is optionally substituted with one or more halo; R 2 is H, C 1-6 alkyl, C 3-10 cycloalkyl, or 3- to 15-membered heterocyclyl; said C 1-6 alkyl of R 2 is optionally substituted with one or more deuterium, halo, —OH, —NH 2 , or C 1-6 alkoxy; said C 3-10 cycloalkyl of R 2 is optionally substituted with one or more —OH; R 3 , if present, is C 1-6 alkyl; L 1 is C 1-6 alkylene; said C 1-6 alkylene of L 1 is optionally substituted with one or more deuterium atoms or C 1-6 alkyl; said C 1-6 alkyl optionally further substituted with one or more —OH or C 1-6 alkoxy; X 2 is N or C(R 5 ); R b is independently at each occurrence selected from the group consisting of —OH, halo, oxo, C 1-6 alkyl, —C(O)—C 1-6 alkyl, —C(O)—NH 2 , —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , —S(O) 2 —R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; said C 1-6 alkyl of R b is optionally substituted with one or more halo, OH, —S(O) 2 —C 1-6 alkyl, or C 3-10 cycloalkyl; said C 3-10 cycloalkyl of said C 1-6 alkyl of R b is optionally further substituted with one or more C 1-6 alkyl or —OH; said C 3-10 cycloalkyl of R b is optionally substituted with one or more —OH, C 3-10 cycloalkyl, or C 1-6 alkyl; said C 1-6 alkyl of said C 3-10 cycloalkyl of R b is optionally further substituted with one or more -OH, deuterium, or halo; R c at each occurrence is independently selected from the group consisting of halo, C 1-6 alkyl, —C(O)—C 1-6 alkyl, —C(O)—NH 2 , —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , —S(O) 2 —R a , C 3-10 cycloalkyl, and 3- to 10-membered heterocyclyl; said C 1-6 alkyl of R c is optionally substituted with one or more —S(O) 2 —C 1-6 alkyl; said C 3-10 cycloalkyl of R c is optionally substituted with one or more —OH or C 1-6 alkyl; said 3- to 10-membered heterocyclyl of R c is optionally substituted with one or more —OH or C 1-6 alkyl; said C 1-6 alkyl of said 3 to 10 membered heterocyclyl of R c is optionally further substituted with one or more —OH; R a is independently at each occurrence: (i) C 1-6 alkyl optionally substituted with one or more halo, —OH, —S(O) 2 —C 1-6 alkyl, or —N(C 1-6 alkyl)-C(O)—C 1-6 alkyl; (ii) C 3-10 cycloalkyl optionally substituted with one or more —OH, —C(O) 2 —C 1-6 alkyl, —C(O)—NH(C 1-6 alkyl), —C(O)—N(C 1-6 alkyl) 2 , or —C(O)—C 3-10 heterocyclyl, or C 1-6 alkyl; the C 1-6 alkyl is optionally substituted with one or more —OH; (iii) a 3- to 10-membered heterocyclyl optionally substituted with one or more C 1-6 alkyls, or (iv) NH(C 1-6 alkyl); R 5 is independently at each occurrence H, halo, —CN, 3- to 10-membered heterocyclyl, C 1-6 alkyl, or C 1-6 alkoxy; said C 1-6 alkyl of R 5 is optionally substituted with one or more halo or —OH; said C 1-6 alkoxy of R 5 is optionally substituted with one or more halo; R 6 and R 7 are each independently H or halo.

2. The compound of claim 1, wherein:

74. The compound of claim 74, wherein the compound is a compound of formula (I-E4): 【Chemistry 245】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. (In the formula, r is an integer from 0 to 1; Y 3 , Y 4 and Y 5 are each independently C or N optionally substituted with one or more H or R c ; Dashed lines represent single or double bonds.) 74. The compound of claim 73, wherein:

75. The compound comprising: 【Chemical 1357-1】 【Chemistry 1357-2】 【Chemistry 1357-3】 【Chemistry 1357-4】 【Chemistry 1357-5】 【Chemistry 1357-6】 【Chemistry 1357-7】 【Chemistry 1357-8】 【Chemistry 1357-9】 【Chemistry 1357-10】 【Chemistry 1357-11】 or a pharmaceutically acceptable salt of any of the foregoing, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

76. A pharmaceutical composition comprising: (i) a compound according to claim 73, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.

77. A composition comprising the compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; or 1. A pharmaceutical composition comprising: (i) a compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients, 1. A composition or pharmaceutical composition for use in a method for inhibiting APOL1 in a cell, The composition or pharmaceutical composition, wherein the method comprises exposing the cell to the composition or pharmaceutical composition.

78. A composition comprising the compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; or 1. A pharmaceutical composition comprising: (i) a compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients, A composition or pharmaceutical composition for treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof, The composition or pharmaceutical composition, wherein the disease, disorder, or condition is selected from the group consisting of chronic kidney disease (CKD), focal segmental glomerulosclerosis (FSGS), kidney disease caused by hypertension, human immunodeficiency virus-associated nephropathy (HIVAN), sickle cell nephropathy, lupus nephritis, diabetic kidney disease, APOL1-associated nephropathy, viral nephropathy, COVID-19-associated nephropathy, preeclampsia, and sepsis.

79. The composition or pharmaceutical composition of claim 78, wherein the disease, disorder, or condition is selected from the group consisting of chronic kidney disease (CKD), focal segmental glomerulosclerosis (FSGS), kidney disease caused by hypertension, human immunodeficiency virus-associated nephropathy (HIVAN), sickle cell nephropathy, lupus nephritis, diabetic kidney disease, APOL1-associated nephropathy, viral nephropathy, and COVID-19-associated nephropathy.

80. The composition or pharmaceutical composition described in claim 78, wherein the disease, disorder, or condition is chronic kidney disease (CKD). (i) a compound according to claim 73, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising a compound according to claim 73, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use in treating an APOL1-mediated disease, disorder, or condition in an individual in need thereof. A kit comprising: The kit, wherein the disease, disorder, or condition is selected from the group consisting of chronic kidney disease (CKD), focal segmental glomerulosclerosis (FSGS), kidney disease caused by hypertension, human immunodeficiency virus-associated nephropathy (HIVAN), sickle cell nephropathy, lupus nephritis, diabetic kidney disease, APOL1-associated nephropathy, viral nephropathy, COVID-19-associated nephropathy, preeclampsia, and sepsis.

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